Submissions for variant NM_000059.4(BRCA2):c.10G>T (p.Gly4Ter)

dbSNP: rs397507571

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000257718	SCV000323955	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2016-10-18	reviewed by expert panel	curation	Variant allele predicted to encode a truncated non-functional protein.
GeneKor MSA	RCV000239090	SCV000296805	pathogenic	not provided	2020-01-01	criteria provided, single submitter	clinical testing	This sequence change is a point mutation that replaces Glycine with a premature termination codon at the fourth position of BRCA2 protein. The resulting protein is truncated and inactive. This variant has been reported in international bibliography in patients with breast and ovarian cancer (PMID: 17453335). This finding is not present in population databases (ExAC, EVS). The mutation database ClinVar contains an entry for this variant (Variation ID: 51063).
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000257718	SCV000326495	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-02	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769679	SCV000901092	pathogenic	Breast and/or ovarian cancer	2019-08-21	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001017301	SCV001178364	pathogenic	Hereditary cancer-predisposing syndrome	2020-11-02	criteria provided, single submitter	clinical testing	The p.G4* pathogenic mutation (also known as c.10G>T), located in coding exon 1 of the BRCA2 gene, results from a G to T substitution at nucleotide position 10. This changes the amino acid from a glycine to a stop codon within coding exon 1. This pathogenic mutation has been reported in numerous families diagnosed with breast and/or ovarian cancer (Konstantopoulou I et al. Breast Cancer Res. Treat. 2008 Feb;107:431-41; Rebbeck TR et al. Hum Mutat. 2018 05;39:593-620; Tsaousis GN et al. BMC Cancer. 2019 Jun;19:535; Apostolou P et al. Int J Cancer. 2020 Sep;147:1334-1342). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). 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.
Clinical Genetics and Genomics, Karolinska University Hospital	RCV000239090	SCV001449876	pathogenic	not provided	2017-01-13	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001384947	SCV001584648	pathogenic	Hereditary breast ovarian cancer syndrome	2020-12-04	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gly4*) 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). For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individuals affected with breast and/or ovarian cancer (PMID: 17453335, 29446198). ClinVar contains an entry for this variant (Variation ID: 51063). This variant is not present in population databases (ExAC no frequency).
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000239090	SCV001906461	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000239090	SCV001959308	pathogenic	not provided		no assertion criteria provided	clinical testing