Submissions for variant NM_007294.4(BRCA1):c.2405_2406del (p.Val802fs)

dbSNP: rs80357706

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000497270	SCV000210022	pathogenic	not provided	2023-06-01	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Identified in individuals with personal or family history of breast or ovarian cancer (Risch et al., 2001; Liede et al., 2002; Carraro et al., 2013; Azzolini et al., 2016; Brianese et al., 2017; Jara et al., 2017; Rashid et al., 2019; Siraj et al., 2019; Hur et al., 2020; Santonocito et al., 2020; Guindalini et al., 2022); Not observed at significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 2524delTG; This variant is associated with the following publications: (PMID: 24884479, 32058061, 20373018, 23469205, 11179017, 27553291, 27062684, 18821011, 12181777, 27836010, 29116469, 25007954, 28985766, 29346284, 27741520, 30720243, 29907814, 11597388, 29922827, 34645131, 35377489, 30825404, 31528241, 32455662, 32438681, 35264596)
Ambry Genetics	RCV000162857	SCV000213344	pathogenic	Hereditary cancer-predisposing syndrome	2022-02-22	criteria provided, single submitter	clinical testing	The c.2405_2406delTG pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of two nucleotides at nucleotide positions 2405 to 2406, causing a translational frameshift with a predicted alternate stop codon (p.V802Efs*7). This alteration has been reported in multiple individuals that meet criteria for hereditary breast and ovarian cancer (HBOC) syndrome (Risch HA et al. Am. J. Hum. Genet. 2001 Mar;68:700-10; Papi L et al. Breast Cancer Res. Treat. 2009 Oct;117:497-504; Carraro DM et al. PLoS ONE. 2013 Mar;8:e57581; Azzollini J et al. Eur. J. Intern. Med. 2016 Jul;32:65-71; Rashid MU et al. BMC Cancer. 2016 08;16:673; Siraj AK et al. Hum Mutat, 2019 06;40:729-733; Santonocito C et al. Cancers (Basel), 2020 May;12:; Vietri MT et al. Eur J Med Genet, 2020 Jun;63:103883). Of note, this alteration is also designated as 2524delTG and c.2401_2402delTG 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.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000111844	SCV000325345	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
A.C.Camargo Cancer Center / LGBM, A.C.Camargo Cancer Center	RCV000412819	SCV000492473	pathogenic	Breast neoplasm		criteria provided, single submitter	research
Color Diagnostics, LLC DBA Color Health	RCV000162857	SCV000683032	pathogenic	Hereditary cancer-predisposing syndrome	2020-01-15	criteria provided, single submitter	clinical testing	This variant deletes 2 nucleotides in exon 10 of the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been identified in 1/250578 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000111844	SCV000744658	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-09-21	criteria provided, single submitter	clinical testing
Mendelics	RCV000496253	SCV000839269	pathogenic	Hereditary breast ovarian cancer syndrome	2018-07-02	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496253	SCV001383223	pathogenic	Hereditary breast ovarian cancer syndrome	2023-10-16	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Val802Glufs*7) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is present in population databases (rs80357706, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 11179017, 20373018, 23469205, 27062684, 29907814). This variant is also known as c.2524delTG. ClinVar contains an entry for this variant (Variation ID: 54558). For these reasons, this variant has been classified as Pathogenic.
Breast Cancer Information Core (BIC) (BRCA1)	RCV000111844	SCV000144409	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2002-05-29	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496253	SCV000587211	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000111844	SCV000733642	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1		no assertion criteria provided	clinical testing