ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.1878A>G (p.Val626=) (rs8176154)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000222216 SCV000275040 likely benign Hereditary cancer-predisposing syndrome 2015-04-01 criteria provided, single submitter clinical testing
GeneDx RCV000438203 SCV000512289 likely benign not specified 2018-03-08 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.
Invitae RCV000533270 SCV000635817 likely benign not provided 2018-11-28 criteria provided, single submitter clinical testing
Color RCV000222216 SCV000682995 likely benign Hereditary cancer-predisposing syndrome 2016-12-06 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000438203 SCV000918725 likely benign not specified 2018-04-06 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.1878A>G alters a non-conserved nucleotide resulting in a synonymous change. Several computational tools predict an impact on normal splicing: Three predict the variant creates a 5 donor site. However, multiple functional studies found the variant to not affect splicing (Anczukow_2008, Baert_2018). The variant was observed with an allele frequency of 5.1e-05 in 277002 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in BRCA1 causing Hereditary Breast and Ovarian Cancer (5.1e-05 vs 0.001), allowing no conclusion about variant significance. The variant, c.1878A>G, has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer. These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. Multiple ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant predominantly as "likely benign" and one as "uncertain significance." Based on the evidence outlined above, the variant was classified as "likely benign."

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