ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4218_4221del (p.Lys1406fs) (rs80359435)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000113285 SCV000300723 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000044372 SCV000072385 pathogenic Hereditary breast and ovarian cancer syndrome 2018-06-12 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys1406Asnfs*3) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with ovarian cancer (PMID: 28541631). This variant is also known as c.4216_4219delAAAG in the literature. ClinVar contains an entry for this variant (Variation ID: 51614). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000044372 SCV000694753 likely pathogenic Hereditary breast and ovarian cancer syndrome 2017-08-07 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.4218_4221delAGAA (p.Lys1406Asnfs) variant (alternatively also known as 4446del4) results in a premature termination codon, predicted to cause a truncated or absent BRCA2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. p.Trp2990X, p.Gln3066X, p.Tyr3098X, etc). This variant is absent in 119932 control chromosomes from ExAC. In literature, this variant has been detected in one ovarian cancer case with somatic origin (Cancer Genome Atlast_2011, Kanchi_2014). However, multiple clinical diagnostic laboratories have reported this variant as a germline occurrence and have classified it as pathogenic. Taken together, this variant is classified as likely pathogenic.
Breast Cancer Information Core (BIC) (BRCA2) RCV000113285 SCV000146392 pathogenic Breast-ovarian cancer, familial 2 2003-12-23 no assertion criteria provided clinical testing

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