Submissions for variant NM_007294.4(BRCA1):c.2210_2211del (p.Thr737fs)

dbSNP: rs80357654

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)	RCV000031037	SCV000299721	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2016-09-08	reviewed by expert panel	curation	Variant allele predicted to encode a truncated non-functional protein.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000047759	SCV000075772	pathogenic	Hereditary breast ovarian cancer syndrome	2023-04-06	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Thr737Serfs*2) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast and ovarian cancer (PMID: 9667259). This variant is also known as 2329delCA. ClinVar contains an entry for this variant (Variation ID: 37456). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV000131875	SCV000186930	pathogenic	Hereditary cancer-predisposing syndrome	2023-11-16	criteria provided, single submitter	clinical testing	The c.2210_2211delCA pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of two nucleotides at nucleotide positions 2210 to 2211, causing a translational frameshift with a predicted alternate stop codon (p.T737Sfs*2). This alteration was identified in a female diagnosed with bilateral breast cancer and ovarian cancer (Frank TS et al. J. Clin. Oncol. 1998; 16:2417-25). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.
GeneDx	RCV000236097	SCV000293471	pathogenic	not provided	2018-02-21	criteria provided, single submitter	clinical testing	This deletion of 2 nucleotides in BRCA1 is denoted c.2210_2211delCA at the cDNA level and p.Thr737SerfsX2(T737SfsX2) at the protein level. The normal sequence, with the bases that are deleted in braces, is GAAA[CA]GTTA. The deletion causes a frameshift, which changes a Threonine to a Serine at codon 737, and creates a premature stop codon at position 2 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA1 c.2210_2211delCA, published as c.2329delCA using alternate nomenclature, was observed in a patient with ovarian and bilateral breast cancer (Frank 1998). We consider this variant to be pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000031037	SCV000325290	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000031037	SCV004839385	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2023-12-07	criteria provided, single submitter	clinical testing	The c.2210_2211del (p.Thr737Serfs*2) variant of the BRCA1 gene creates an early stop codon. It is expected to result in an absent or disrupted protein product. This variant has been reported in an individual with breast and ovarian cancer (PMID: 9667259). ClinVar contains an entry for this variant (ID: 37456). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Truncating variants in BRCA1 gene are known to be pathogenic (PMID: 21989022, 17661172, 22762150). Therefore the c.2210_2211del (p.Thr737Serfs*2) variant of the BRCA1 gene is classified as pathogenic.
Sharing Clinical Reports Project (SCRP)	RCV000031037	SCV000053631	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2012-05-08	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000031037	SCV000144337	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	1997-11-14	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000047759	SCV000587199	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research
BRCAlab, Lund University	RCV000031037	SCV004244098	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2020-03-02	no assertion criteria provided	clinical testing