ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.314T>G (p.Leu105Ter)

dbSNP: rs80358561
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Total submissions: 10
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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) RCV000077293 SCV000282376 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics RCV000219806 SCV000276405 pathogenic Hereditary cancer-predisposing syndrome 2022-08-02 criteria provided, single submitter clinical testing The p.L105* pathogenic mutation (also known as c.314T>G), located in coding exon 2 of the BRCA2 gene, results from a T to G substitution at nucleotide position 314. This changes the amino acid from a leucine to a stop codon within coding exon 2. This mutation has been reported in one HBOC family (Thiffault I et al. Br. J. Cancer. 2004 Jan;90:483-91) and has been seen in two Australian patients diagnosed with triple negative breast cancer at 46 and 89 years old, respectively (Wong-Brown MW et al. Breast Cancer Res. Treat. 2015 Feb;150:71-80). This alteration was also identified in a large, worldwide study of BRCA1/2 mutation positive families (Rebbeck TR et al. Hum. Mutat. 2018 05;39:593-620). 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.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077293 SCV000326816 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2015-10-02 criteria provided, single submitter clinical testing
Cancer Genetics and Genomics Laboratory, British Columbia Cancer Agency RCV000496591 SCV000586915 pathogenic Hereditary breast ovarian cancer syndrome 2017-04-18 criteria provided, single submitter clinical testing
Invitae RCV000496591 SCV002234051 pathogenic Hereditary breast ovarian cancer syndrome 2023-09-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu105*) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. 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 premature translational stop signal has been observed in individual(s) with clinical features of HBOC syndrome (PMID: 14735197, 25682074, 29446198). ClinVar contains an entry for this variant (Variation ID: 51406). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV003473324 SCV004212833 pathogenic Familial cancer of breast 2022-03-03 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077293 SCV000109090 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2009-02-28 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077293 SCV000146563 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2002-05-29 no assertion criteria provided clinical testing
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735536 SCV000863674 pathogenic Breast and/or ovarian cancer 2000-12-05 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001358503 SCV001554256 uncertain significance not provided no assertion criteria provided clinical testing

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