ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3365del (p.Gly1122fs) (rs786202160)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164839 SCV000215522 pathogenic Hereditary cancer-predisposing syndrome 2017-02-15 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000241513 SCV000300628 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000482439 SCV000566713 pathogenic not provided 2015-05-27 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA2 is denoted c.3365delG at the cDNA level and p.Gly1122GlufsX28 (G1122EfsX28) at the protein level. The normal sequence, with the base that is deleted in braces, is TCAG[G]AAGT. The deletion causes a frameshift, which changes a Glycine to a Glutamic Acid at codon 1122, and creates a premature stop codon at position 28 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. we consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000781109 SCV000918946 pathogenic Hereditary breast and ovarian cancer syndrome 2018-08-20 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.3365delG (p.Gly1122GlufsX28) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (eg. p.Leu1152X, p.Phe1182fsX1, p.Lys1191fsX6). The variant was absent in 244850 control chromosomes. c.3365delG has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Wei_2018). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and all classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.