ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.2833_2834insTT (p.Lys945fs) (rs80359355)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000216259 SCV000273782 pathogenic Hereditary cancer-predisposing syndrome 2015-01-26 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000113098 SCV000146123 pathogenic Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Color RCV000216259 SCV000688775 pathogenic Hereditary cancer-predisposing syndrome 2016-04-25 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000113098 SCV000326772 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000113098 SCV000300564 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000657374 SCV000779107 pathogenic not provided 2018-05-15 criteria provided, single submitter clinical testing This insertion of two nucleotides in BRCA2 is denoted c.2833_2834insTT at the cDNA level and p.Lys945IlefsX16 (K945IfsX16) at the protein level. The normal sequence, with the bases that are inserted in brackets, is TAAAA[insTT]AAGA. The insertion causes a frameshift which changes a Lysine to an Isoleucine at codon 945, and creates a premature stop codon at position 16 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000590074 SCV000694629 pathogenic Hereditary breast and ovarian cancer syndrome 2016-09-26 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.2833_2834insTT (p.Lys945Ilefs) variant 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.c.2957dupA/p.Asn986fs). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 120672 control chromosomes however has been reported in 5 patients in BIC (4 from Myriad). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000590074 SCV000759110 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys945Ilefs*16) 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 reported in individuals in the Breast Cancer Information Core database (PMID: 10923033). ClinVar contains an entry for this variant (Variation ID: 125995). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.

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