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

dbSNP: rs80358561

Total submissions: 10

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