Submissions for variant NM_000059.4(BRCA2):c.5823del (p.Val1942fs)

dbSNP: rs80359540

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)	RCV000113489	SCV000300936	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.
Ambry Genetics	RCV000217033	SCV000278044	pathogenic	Hereditary cancer-predisposing syndrome	2023-08-05	criteria provided, single submitter	clinical testing	The c.5823delA pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a deletion of one nucleotide at nucleotide position 5823, causing a translational frameshift with a predicted alternate stop codon (p.V1942Ffs*21). This mutation was described in a Swedish HBOC family in which the father and four of his sons were diagnosed with prostate cancer between the ages of ages of 51 and 63, and three daughters were diagnosed with breast cancer between the ages of 47 and 61 (Gronberg, H et al. Genes Chromosomes Cancer. 2001 Mar;30(3):299-301). This mutation was also detected in a male diagnosed with breast cancer at age 58 (Tai, YC et al. J Natl Cancer Inst. 2007 Dec 5;99(23):1811-4). This variant is considered to be rare based on population 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.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000113489	SCV000327290	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-02	criteria provided, single submitter	clinical testing
Clinical Genetics and Genomics, Karolinska University Hospital	RCV001269662	SCV001449815	pathogenic	not provided	2015-04-30	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001852945	SCV002237270	pathogenic	Hereditary breast ovarian cancer syndrome	2024-05-26	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Val1942Phefs*21) 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 breast and/or ovarian cancer (PMID: 10644434, 29084914). This variant is also known as 6051delA. ClinVar contains an entry for this variant (Variation ID: 51945). For these reasons, this variant has been classified as Pathogenic.
Clinical Genetics Laboratory, Skane University Hospital Lund	RCV001269662	SCV005199794	pathogenic	not provided	2022-05-27	criteria provided, single submitter	clinical testing
OMIM	RCV000009918	SCV000030139	pathogenic	Malignant tumor of prostate	2001-03-01	no assertion criteria provided	literature only
Breast Cancer Information Core (BIC) (BRCA2)	RCV000113489	SCV000146706	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2		no assertion criteria provided	clinical testing
BRCAlab, Lund University	RCV000113489	SCV002588894	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2022-08-26	no assertion criteria provided	clinical testing