ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6875A>G (p.Glu2292Gly) (rs397507378)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131009 SCV000185935 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-12 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV000460823 SCV000549571 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-09-03 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glycine at codon 2292 of the BRCA2 protein (p.Glu2292Gly). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. This variant is present in population databases (rs397507378, ExAC 0.002%). This variant has been reported in an individual affected with breast cancer (PMID: 27616075). ClinVar contains an entry for this variant (Variation ID: 38071). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000120350 SCV000592081 uncertain significance not specified criteria provided, single submitter clinical testing
Color RCV000131009 SCV000683824 uncertain significance Hereditary cancer-predisposing syndrome 2020-01-21 criteria provided, single submitter clinical testing
Counsyl RCV000031653 SCV000785503 uncertain significance Breast-ovarian cancer, familial 2 2017-08-22 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000755861 SCV000883486 uncertain significance not provided 2017-07-12 criteria provided, single submitter clinical testing The BRCA2 c.6875A>G;p.Glu2292Gly variant has been published in at least one individual with breast cancer (Kraus 2017). The variant is listed in the ClinVar database (Variation ID: 38071) and in the dbSNP variant database (rs397507378) with an allele frequency of 0.001453 percent (4/275354 alleles) in the Genome Aggregation Database. The amino acid at this position is highly conserved across species and computational algorithms (PolyPhen2, SIFT) predict this variant is damaging. Considering available information, there is insufficient evidence to classify this variant with certainty. References: Kraus C et al. Gene panel sequencing in familial breast/ovarian cancer patients identifies multiple novel mutations also in genes others than BRCA1/2. Int J Cancer. 2017 Jan 1;140(1):95-102.
Integrated Genetics/Laboratory Corporation of America RCV000120350 SCV000917048 uncertain significance not specified 2018-11-01 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.6875A>G (p.Glu2292Gly) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.5e-05 in 275354 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.6875A>G has been reported in the literature in an individual affected with triple negative breast cancer (Kraus_2016). This report does not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000755861 SCV001133878 uncertain significance not provided 2019-06-23 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031653 SCV000054260 uncertain significance Breast-ovarian cancer, familial 2 2013-05-29 no assertion criteria provided clinical testing
ITMI RCV000120350 SCV000084502 not provided not specified 2013-09-19 no assertion provided reference population

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