ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3225T>C (p.Ser1075=) (rs779228375)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163364 SCV000213901 likely benign Hereditary cancer-predisposing syndrome 2014-09-17 criteria provided, single submitter clinical testing
Color RCV000163364 SCV000683536 likely benign Hereditary cancer-predisposing syndrome 2016-11-14 criteria provided, single submitter clinical testing
Counsyl RCV000410435 SCV000488671 likely benign Breast-ovarian cancer, familial 2 2016-05-25 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000410435 SCV000579071 likely benign Breast-ovarian cancer, familial 2 2017-06-29 reviewed by expert panel curation Synonymous substitution variant, with low bioinformatic likelihood to result in a splicing aberration (Splicing prior probability 0.02; http://priors.hci.utah.edu/PRIORS/).
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735539 SCV000863677 uncertain significance Breast and/or ovarian cancer 2014-09-15 no assertion criteria provided clinical testing
GeneDx RCV000419823 SCV000512353 likely benign not specified 2017-05-29 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Integrated Genetics/Laboratory Corporation of America RCV000206590 SCV000494406 uncertain significance Hereditary breast and ovarian cancer syndrome 2016-04-14 criteria provided, single submitter clinical testing Variant summary: The c.3225T>C variant affects a non-conserved nucleotide, resulting in no amino acid change. One in-silico tool predicts benign outcome for this variant. 5/5 programs in Alamut predict that this variant does not affect normal splicing. ESE finder predicts that this variant may affect ESE site of SRp55. However, these predictions are not confirmed by experimental studies. This variant is found in 3/119346 control chromosomes at a frequency of 0.0000251, which does not exceed maximal expected frequency of a pathogenic allele (0.0007503). In addition, multiple clinical laboratories classified this variant as likely benign, however, without evidence for independent review. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant was classified as VUS-possibly benign.
Integrated Genetics/Laboratory Corporation of America RCV000590819 SCV000694678 uncertain significance not provided 2017-08-16 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.3225T>C (p.Ser1075Ser) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a benign outcome for this variant. 5/5 programs in Alamut predict that this variant does not affect normal splicing. ESE finder predicts that this variant may generate a binding site for SRp55 splicing factor. However, these predictions are not confirmed by experimental studies. This variant was found in 3/119346 control chromosomes at a frequency of 0.0000251, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). One study reported the variant in an individual with personal or family history with breast and/or ovarian cancer, however without strong evidence for causality (Barrios, Familial Cancer, 2017). In addition, multiple clinical diagnostic laboratories/reputable databases in ClinVar have classified this variant as likely benign. Taken together, this variant is classified as VUS-possibly benign.
Invitae RCV000206590 SCV000260960 likely benign Hereditary breast and ovarian cancer syndrome 2018-01-03 criteria provided, single submitter clinical testing

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