r/ClinicalGenetics

Hey everyone I indexed through my SV and CNV files and found the below findings. To my knowledge this means I had SV deletions that were the length listed at the locations in the genes. I am uncertain about the significance of this information so if anyone was able to provide insight, I would be appreciative. I used the LUMPY CANVAS MANTA and ANOTSV linux open source software applications to go through these files. this is what came up.

2. SULT1A1/SULT1A2-region

   MantaDEL PASS

   chr16:28,597,997–28,611,011

   GT=0/1

   GQ=655

   PR=21,11

   SR=39,13

   IGV reciprocal discordant pairs

   Depth \~35.06x; flanks \~33.02x/\~33.33x

   AnnotSV SULT1A1 CDS overlap 906 bp / 100%

   Frameshift: no

   ACMG 3

3. PIAS1

   MantaDEL PASS

   chr15:68,133,664–68,136,607

   GT=1/1

   GQ=103

   PR=0,25

   SR=0,26

   AnnotSV intron2-intron2

   CDS overlap 0

   ACMG 3

4. ESR1

   MantaDEL PASS

   chr6:152,068,854–152,071,103

   GT=0/1

   GQ=356

   PR=12,3

   SR=27,10

   AnnotSV intron8-intron8

   CDS overlap 0

   ACMG 3

5. UGT1A cluster

   MantaDEL PASS

   chr2:233,722,831–233,725,356

   GT=0/1

   GQ=93

   PR=3,8

   SR=12,15

   AnnotSV intronic across UGT1A8/10/9/7/6/5/4

   CDS overlap 0

   ACMG 1

6. FKBP5 Manta

   MantaDEL PASS

   chr6:35,658,655–35,661,969

   GT=0/1

   GQ=352

   PR=15,6

   SR=22,12

   AnnotSV intron1/5'UTR

   CDS overlap 0

   B\_loss\_AFmax 0.6895

   ACMG 1

7. SUMF1-region / LOC102723512

   MantaDEL PASS

   chr3:4,025,240–4,027,884

   GT=1/1

   GQ=56

   PR=0,12

   SR=0,22

   AnnotSV LOC102723512 intron1/UTR

   CDS overlap 0

   ACMG 1

8. CHD2

   Canvas gain/PASS signal

   Depth region \~41.87x

   Flanks \~35.53x/\~35.63x

   Ratio \~1.18x

9. SLC22A3

   Manta breakpoint-near-gene candidate

   Region depth \~31.69x

   Flanks \~33.43x/\~31.01x

10. THRB

LUMPY INV

chr3:24,264,558–24,264,604

Size \~45 bp

SU=5

PE=1

SR=4

Hello, I’m finding myself a bit stuck as far as getting assessed for EDS or vEDS. I’ve sought further assessment after having an MRI that showed a Dolichoectasia (enlongated/stretched/tortuous) of my right anterior-inferior cerebellar artery in my late 30s. As a person with varicose veins since early 20s, plus other related symptoms, I started to look at testing options. My desire to seek further testing is mainly because I have two young children, one of whom has low tone. I’m finding that it’s pretty tough in our BC health system to get any type of follow up, and seems like only private genetic testing at $1k+ is an option. Any info about access points for assessment regarding connective tissue disorders or genetic testing is welcome. Thank you.

BRCA1 gene mutations can lead to increased risk for cancer.

Germline mutations in the BRCA1 gene can be passed on to people that will then become carriers of the faulty gene.

The lifetime risk to develop an associated cancer (breast cancer, ovarian cancer etc. ) for someone carrying this heterozygous defect is very high (around 60%). Since they already have one faulty gene, they are more susceptible for the 2nd gene to become faulty as well (the two hit hypothesis), and thus these inherited cancers have an earlier onset too.

How come there is such a stagerring risk (60%) for a person to develop cancer when one of their alleles is fine? Spontaneous mutation chances alone surely cannot accound for the entire risk as they are quite rare, (right?)

**Even though tumor suppressor genes are recessive on a cellular level, why are the phenotypes (the expression of cancer) effectively dominant?**

a question i'm sure has been posted many times in this sub but i'm looking for more specific advice. i've been going back and forth on the two for the last four years during my undergrad, i felt like i finally decided but now i'm doing this seminar in genetic counseling subjects over the summer and i'm thinking it over again.

on the one hand, i want to be a doctor, i'm interested in science and medicine, i want to be an expert in genetics (prenatal/pedes specifically), and i want to be a leader.

but on the other hand, i love working with families, i really enjoy learning more about them and taking a family history, and i enjoy the counseling part of genetic counseling and i want to help explain things and teach families about the condition their child has.

i guess the thing i'm worried about is that i won't get to do those things as a geneticist. i've had a lot of trouble finding anyone to shadow, geneticist or genetic counselor. i live somewhat near a large teaching hospital, but they are funny about letting people shadow either field, so i figure this is the next best thing. thanks for any advice in advance!

Hi everyone,

I'm looking for other parents who may have gone through something similar because lately I've been feeling very alone.

I'm overwhelmed by the lack of answers and keep finding myself endlessly Googling everything.

My son is 22 months old and has several medical conditions. He has hypotonia, severe hydronephrosis (he's scheduled for kidney surgery next week), had surgery for an undescended testicle when he was one year old, and also has hemihypotrophy/hemihypertrophy affecting his left side.

His left leg is shorter, his left foot is smaller, and he has problems with his left hip. Basically, everything on his left side is affected.

Because of the poor public healthcare system in our country, we didn't get the full picture early on. Instead, we've had to piece everything together over time. It all started when he was 11 months old with the hypotonia diagnosis, and the most recent discovery was his kidney problem.

We're currently waiting for the results of genetic testing, as his doctors are trying to determine whether all of these findings could be part of an underlying genetic syndrome.

I'm wondering if anyone has a child with a similar combination of conditions, or if these kinds of findings ended up being connected by an underlying diagnosis. We've had various tests done, but we're still searching for answers.

I'd really appreciate hearing from anyone who has gone through something similar, even if your child's situation isn't exactly the same.

Right now, I just feel very alone in all of this...

I have a brother with ID which is of unknown origin. I recently bought a direct to customer with no use. No clinical geneticist in my country was trained to understand it. They suggested the USA. How does one go about getting their gene sequenced? Im a foreigner so if anyone has advice to that, it will be best.

I’m wondering how to go about getting genetic testing done immediately after my baby is born (and what kind of genetic testing would be offered). I had a low risk NIPT and no soft markers on any growth scans and my baby has had an IUGR diagnosis since 24 weeks. My MFM offered an amnio but has not stated she is concerned despite no plausible cause of our IUGR at this point. Baby’s head has been between <1%-4% since 20 weeks anatomy scan but has maintained normal sized long bones. The abdomen is also in the 2%-7% range consistently. No one has referred us to a genetic counselor.

CW: Miscarriage

My partner (28m) and I (29f) have been trying to have a baby for three years. I've been pregnant 6 times now, currently pregnant with the 6th) and have never made it past 7.5weeks. After years of testing from both me and my partner, all of the specialists I've seen have no answers as to why I keep having early losses.

In 2020 I found out I have the ATM gene mutation which is linked to breast, ovarian, pancreatic, and prostate cancer. My dad was diagnosed that year with prostate cancer and the ATM mutation, which led me to get tested as well.

Every doctor and OBGYN I've spoken with has no idea what the gene mutation is and assumes it has nothing to do with my miscarriages, and the genetics team I met with said there isn't enough research currently to know if the two are connected.

I'm convinced my ovaries have been affected by the ATM mutation in some way and that it must be why I can't stay pregnant.

I'm just trying to do my own research now and see if anyone else has had this unique combination of health concerns?

TL;DR Anyone out there also have the ATM gene mutation and recurrent pregnancy loss??

Hi all,

I’m trying to understand the differences between the following prenatal tests:

- FISH
- QF-PCR
- karyotype
- aCGH array (CMA)
- SNP array (CMA)

After a high risk NIPT for T21, they ordered a combination of QF-PCR, SNP array and karyotype for me. Culture cell due to maternal cell contamination. QF-PCR came back normal, SNP returned 8% mosaicism.

Is there a specialist here who can explain to me the differences between the tests above in terms of (1) method/classification, (2) number of cells, (3) effect of cell culture, (4) detection thresholds and sensitivity/specificity, (5) fit for low-grade mosaicism?

I feel I have some basic knowledge by now but I seem to be reading some conflicting information, especially about the impact of cell culture and low-grade mosaicism.

Any insights would be greatly appreciated!

Hi everyone! I (26 YOF) am currently 17 weeks pregnant my second baby boy and wanted to ask if anyone here has seen a similar circumstance to mine. My first boy is 12 months old and completely healthy.

My NIPT LabCorp blood draw was at 10 weeks 2 days pregnant and the fetal fraction was 20%. PPV 66%. The results were flagged as abnormal for T21 (Down Syndrome) but it was considered a “low-mosaic” pattern, so they believe it may be confined placental mosaicism or I had vanishing twin syndrome. Or my baby could have low mosaic T21 which comprises roughly 1-2% of all babies diagnosed with T21.

The genetic counselor told me that the cut off for LabCorp even flagging this as a high risk is 19% of the cells showing an extra copy of chromosome 21. And my sample had 22% of the cells affected. That’s why she suspected this result may not truly represent fetal mosaicism and may be resulting from some other source.

At 13 weeks I had an early anatomy ultrasound with no soft markers for T21. At 16 weeks I had another ultrasound revealing an echogenic bowel, but it was otherwise a normal ultrasound with no other soft markers.

I had an amniocentesis at 16 weeks. FISH results came back completely normal. All 50/50 cells tested were negative for anomalies of chromosome X, Y, 13, 18, and 21. I’m still waiting the karyotype and microarray results.

Unfortunately, the hospital messaged me saying they had enough fetal DNA in the amnio sample to run the FISH and karyotype, but not the uncultured SNP microarray. They said for the microarray, the cells would need to be cultured but that could potentially skew the results in the case of mosaicism. They also told me it’s going to add 4-6 weeks to the results timeline which is frustrating.

Has anyone seen FISH results be completely normal for T21 but ended up having a low level mosaic result in the karyotype or microarray? My genetic counselor said it’s uncommon but not unheard of for this to happen after a normal FISH. Anyone know the stats on that?