ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.8981C>T (p.Ser2994Leu)

dbSNP: rs1566253076
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneKor MSA RCV000708686 SCV000821949 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001050996 SCV001215129 uncertain significance Hereditary breast ovarian cancer syndrome 2023-02-06 criteria provided, single submitter clinical testing Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA2 protein function. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 584513). This missense change has been observed in individual(s) with BRCA2-related conditions (PMID: 31159747). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 2994 of the BRCA2 protein (p.Ser2994Leu).
GeneDx RCV001759425 SCV002007703 uncertain significance not provided 2023-06-05 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; In silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown; Observed in an individual undergoing hereditary cancer panel testing (Tsaousis et al., 2019); Also known as 9209C>T; This variant is associated with the following publications: (PMID: 31911673, 12228710, 31159747)

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