ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8979_8982inv (p.Ser2994Asp)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000223004 SCV000275464 uncertain significance Hereditary cancer-predisposing syndrome 2015-04-24 criteria provided, single submitter clinical testing The c.8979_8982delATCAinsTGAT variant (also known as 9207del4insTGAT and p.S2994D), located in coding exon 22 of the BRCA2 gene, results from a deletion of ATCA and insertion of TGAT between nucleotide positions 8979 and 8982. The serine at codon 2994 is replaced by aspartic acid, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6498 samples (12996 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 150000 alleles tested) in our clinical cohort. This amino acid position is not well conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of c.8979_8982delATCAinsTGAT remains unclear.
Invitae RCV000693673 SCV000821551 uncertain significance Hereditary breast ovarian cancer syndrome 2018-05-25 criteria provided, single submitter clinical testing This sequence change replaces serine with aspartic acid at codon 2994 of the BRCA2 protein (p.Ser2994Asp). The serine residue is moderately conserved and there is a small physicochemical difference between serine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 231569). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Color Diagnostics, LLC DBA Color Health RCV000223004 SCV004362786 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-29 criteria provided, single submitter clinical testing This variant is a 4-basepair substitution that results in a single amino acid change replacing serine with aspartic acid at codon 2994 of the BRCA2 protein. This 4-basepair substitution is also known as an inversion, chr13.GRCh37:g.32953912_32953915inv and c.8979_8982inv. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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