ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.8988_8990delinsTT (p.Leu2996fs)

dbSNP: rs397508027
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Total submissions: 5
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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) RCV000241303 SCV000301331 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Labcorp Genetics (formerly Invitae), Labcorp RCV000045681 SCV000073694 pathogenic Hereditary breast ovarian cancer syndrome 2015-08-10 criteria provided, single submitter clinical testing This sequence change deletes 3 nucleotides and inserts 2 nucleotides in exon 23 of the BRCA2 mRNA (c.8988_2990delATAinsTT), causing a frameshift at codon 2996. This creates a premature translational stop signal (p.Leu2996Phefs*5) and is expected to result in an absent or disrupted protein product. Truncating variants in BRCA2 are known to be pathogenic. This particular truncation has been reported in the literature (PMID: 19616529). This variant is also known as c.9216_9218delATAinsTT in the literature. For these reasons, this variant has been classified as Pathogenic.
Genologica Medica RCV000241303 SCV000577972 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2017-01-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV000509596 SCV000608172 pathogenic Hereditary cancer-predisposing syndrome 2021-03-03 criteria provided, single submitter clinical testing The c.8988_8990delATAinsTT pathogenic mutation, located in coding exon 22 of the BRCA2 gene, results from the deletion of 3 nucleotides and insertion of two nucleotides at positions 8988 to 8990, causing a translational frameshift with a predicted alternate stop codon (p.L2996Ffs*5). This variant has been identified in individuals with a personal and/or family history suspicious for Hereditary Breast and Ovarian Cancer syndrome, including male patients with breast cancer (Jiménez Ide J et al, Clin. Biochem. 2009 Oct;42:1572-6; Esteban Cardeñosa E et al. Breast Cancer Res Treat, 2010 May;121:257-60; de Juan Jiménez I et al. Fam Cancer, 2013 Dec;12:767-77; de Juan I et al. Fam Cancer, 2015 Dec;14:505-13; Pajares B et al. BMC Cancer, 2018 Jun;18:647). Of note, this alteration is also designated as 9216_9218delATAinsTT in published literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001283945 SCV001469462 pathogenic not provided 2020-01-21 criteria provided, single submitter clinical testing This frameshift variant causes the premature termination of BRCA2 protein synthesis. In addition, it has been reported in a family affected with breast cancer in the published literature (PMID: 19616529 (2009)). Based on the available information, this variant is classified as pathogenic.

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