ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9738C>T (p.Ala3246=) (rs80359811)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000114161 SCV000578006 benign Breast-ovarian cancer, familial 2 2017-06-29 reviewed by expert panel curation Synonymous substitution variant, with low bioinformatic likelihood to alter mRNA splicing (splicing prior 0.02; and frequency 0.0025 (Admixed American/Latino), derived from ExAC (2014-12-17).
Invitae RCV000045894 SCV000073907 benign Hereditary breast and ovarian cancer syndrome 2020-12-06 criteria provided, single submitter clinical testing
GeneDx RCV000212291 SCV000167423 benign not specified 2014-03-10 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.
Ambry Genetics RCV000162800 SCV000213281 likely benign Hereditary cancer-predisposing syndrome 2014-06-18 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Color Health, Inc RCV000162800 SCV000684090 likely benign Hereditary cancer-predisposing syndrome 2016-11-18 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000212291 SCV000916938 likely benign not specified 2017-11-24 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.9738C>T (p.Ala3246Ala) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts this variant may affect binding of multiple ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 66/277196 control chromosomes (gnomAD, Ruiz-Flores_2002), predominantly observed in the Latino subpopulation at a frequency of 0.001889 (65/34416). This frequency is about 3 times the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503), suggesting this is likely a benign polymorphism found primarily in the populations of Latino origin. The variant was reported as a polymorphism found in three Mexican HBOC patients in literature, however without strong evidence supporting the benign classification. Multiple clinical labs have classified this variant as likely benign/benign. In one internal sample, this variant co-occurred with a pathogenic variant BRCA1 c.68_69delAG, further supporting the benign outcome. Taken together, this variant is classified as Likely Benign.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001283661 SCV001159022 likely benign none provided 2020-06-08 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000114161 SCV000147708 uncertain significance Breast-ovarian cancer, familial 2 2003-10-29 no assertion criteria provided clinical testing

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