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

dbSNP: rs80357654

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)	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.
Invitae	RCV000047759	SCV000075772	pathogenic	Hereditary breast ovarian cancer syndrome	2023-04-06	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 37456). This variant is also known as 2329delCA. This premature translational stop signal has been observed in individual(s) with breast and ovarian cancer (PMID: 9667259). This variant is not present in population databases (gnomAD no frequency). 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).
Ambry Genetics	RCV000131875	SCV000186930	pathogenic	Hereditary cancer-predisposing syndrome	2014-02-11	criteria provided, single submitter	clinical testing	​The c.2210_2211delCA pathogenic mutation (also known as 2329delCA), located in coding exon 9 of the BRCA1 gene, results from a deletion of two nucleotides between positions 2210 and 2211, causing a translational frameshift with a predicted alternate stop codon. 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). In addition to the clinical data presented in the literature, since frameshifts are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).
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
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