ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.672_681+23del

dbSNP: rs1555281357
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000532479 SCV000635523 pathogenic Hereditary breast ovarian cancer syndrome 2024-05-06 criteria provided, single submitter clinical testing This variant results in the deletion of part of exon 8 of the BRCA2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 462411). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV001025576 SCV001187789 uncertain significance Hereditary cancer-predisposing syndrome 2022-06-06 criteria provided, single submitter clinical testing The c.672_681+23DEL33 variant results from a deletion of 33 nucleotides starting at position 672 in coding exon 7 and extending 23 nucleotides into intron 7 of the BRCA2 gene. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested; however a significant portion of the transcript is in-frame (Ambry internal data). This in-frame transcript, referred to as Δ(E6Q39_E8) in the literature, has been shown to perform complementation in mouse embryonic stem cells and maintains 90% activity in a homology-directed repair functional assay (Mesman, RLS et al. Genet Med 2020 08;22(8):1355-1365). Since supporting evidence is conflicting at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV004767350 SCV005375947 uncertain significance not provided 2023-12-07 criteria provided, single submitter clinical testing In-frame transcript, E6Q39_E8, able to complement growth in mouse embryonic stem cells, leading to homology-directed repair activity comparable to wild-type (PMID: 32398771); Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 32398771)

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