ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4738_4739TG[3] (p.Glu1581fs) (rs864622401)

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Total submissions: 8
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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) RCV000241010 SCV000300780 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 RCV000206526 SCV000260489 pathogenic Hereditary breast and ovarian cancer syndrome 2018-06-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu1581Valfs*37) 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). Loss-of-function variants in BRCA2 are known to be pathogenic. This particular variant has been reported in individuals affected with breast cancer (PMID: 20859677, 23469205). This variant is also known as 4969_4970insTG or 4968insGT in the literature. ClinVar contains an entry for this variant (Variation ID: 220160). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000241010 SCV000327077 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
A.C.Camargo Cancer Center / LGBM, A.C.Camargo Cancer Center RCV000413237 SCV000492468 pathogenic Neoplasm of the breast criteria provided, single submitter research
Baylor Genetics RCV000476565 SCV000541002 pathogenic Familial cancer of breast 2017-02-23 criteria provided, single submitter clinical testing
GeneDx RCV000483210 SCV000568468 pathogenic not provided 2017-09-28 criteria provided, single submitter clinical testing This duplication of 2 nucleotides in BRCA2 is denoted c.4740_4741dupTG at the cDNA level and p.Glu1581ValfsX37 (E1581VfsX37) at the protein level. The normal sequence, with the bases that are duplicated in braces, is CATG[TG]AGAC. The duplication causes a frameshift which changes a Glutamic Acid to a Valine at codon 1581, and creates a premature stop codon at position 37 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA2 c.4740_4741dupTG, also known as 4970insTG, 4968insGT and 4970_4971insTG using alternate nomenclature, has been reported in association with breast cancer (Gallardo 2006, Carraro 2013). We consider this variant to be pathogenic.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000206526 SCV000591924 pathogenic Hereditary breast and ovarian cancer syndrome criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000483210 SCV000600604 pathogenic not provided 2017-07-18 criteria provided, single submitter clinical testing

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