ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.5813G>C (p.Gly1938Ala) (rs41293499)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129261 SCV000184021 uncertain significance Hereditary cancer-predisposing syndrome 2020-10-06 criteria provided, single submitter clinical testing The p.G1938A variant (also known as c.5813G>C), located in coding exon 10 of the BRCA2 gene, results from a G to C substitution at nucleotide position 5813. The glycine at codon 1938 is replaced by alanine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV000657051 SCV000279422 uncertain significance not provided 2020-11-04 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Invitae RCV000257904 SCV000549550 likely benign Hereditary breast and ovarian cancer syndrome 2020-12-07 criteria provided, single submitter clinical testing
Color Health, Inc RCV000129261 SCV000911399 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-08 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000168583 SCV000918976 uncertain significance not specified 2017-12-11 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.5813G>C (p.Gly1938Ala) variant involves the alteration of a non-conserved nucleotide. 3/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 4/245820 control chromosomes (gnomAD) at a frequency of 0.0000163, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. The variant of interest has not, to our knowledge, been reported in affected individuals via publications; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS).
Sharing Clinical Reports Project (SCRP) RCV000076942 SCV000108739 likely benign Breast-ovarian cancer, familial 2 2012-07-23 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000657051 SCV000592003 likely benign not provided no assertion criteria provided clinical testing The p.Gly1938Ala variant was not identified in the literature but was identified in dbSNP (ID:rs41293499 ) “With probable-non-pathogenic allele”. The p.Gly1938Ala variant was classified as a likely benign variant by the Sharing Clinical Reports Project (SCRP) (submitted within the ClinVar database and derived from Myriad reports). The p.Gly1938 residue is not conserved in mammals and the variant amino acid alanine (Ala) is present in opossum, increasing the likelihood that this variant does not have clinical significance. Computational analyses (PolyPhen-2, SIFT, AlignGVGD, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as predicted benign.

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