ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.1106_1108del (p.Asp369del) (rs80358325)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 10
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000195341 SCV000075356 benign Hereditary breast and ovarian cancer syndrome 2017-12-13 criteria provided, single submitter clinical testing
Ambry Genetics RCV000130879 SCV000185784 likely benign Hereditary cancer-predisposing syndrome 2017-09-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Co-occurence with mutation in same gene (phase unknown),Other data supporting benign classification,Seen in trans with a mutation or in homozygous state in individual without severe disease for that gene
GeneDx RCV000047343 SCV000209921 likely benign not specified 2018-03-08 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Counsyl RCV000111551 SCV000220342 likely benign Breast-ovarian cancer, familial 1 2014-05-21 criteria provided, single submitter literature only
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000768648 SCV000324808 likely benign Breast and/or ovarian cancer 2015-09-16 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000047343 SCV000591316 likely benign not specified 2014-04-15 criteria provided, single submitter clinical testing
Color RCV000130879 SCV000682936 likely benign Hereditary cancer-predisposing syndrome 2015-10-01 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000047343 SCV000698832 likely benign not specified 2018-10-12 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.1106_1108delATG (p.Asp369del) results in an in-frame deletion that is predicted to remove an Asp amino acid from the encoded protein. The variant allele was found at a frequency of 5.3e-05 in 245906 control chromosomes, predominantly at a frequency of 0.00012 within the Non-Finnish European subpopulation in the gnomAD database. This frequency is not significantly higher than expected for a pathogenic variant in BRCA1 causing Hereditary Breast and Ovarian Cancer (5.3e-05 vs 0.001), allowing no conclusion about variant significance. c.1106_1108delATG has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Chenevix-Trench_2006) that indicates the variant co-occurred in trans with a pathogenic BRCA1 variant, although the variant was not specified. These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. Co-occurrences with other pathogenic variant(s) have been reported (BRCA2 c.4409_4410delTA, p.I470fsX11; BRCA2 c.7180A>T, p.Arg2394X), providing supporting evidence for a benign role. Multifactorial probability models, performing systematic assessments of variants of unknown significance in the BRCA genes, which included analysis of co-occurrence in trans with known deleterious mutations, personal and family history of cancer and co-segregation with disease in pedigrees (when available), predicted this variant to be neutral (Easton 2007, Lindor 2012). Five ClinVar submissions from other clinical diagnostic laboratories (evaluation after 2014) cite the variant as likely benign/benign. Based on the evidence outlined above, the variant was classified as likely benign.
Breast Cancer Information Core (BIC) (BRCA1) RCV000111551 SCV000144013 uncertain significance Breast-ovarian cancer, familial 1 2013-03-25 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000782126 SCV000916303 likely benign Ovarian cancer no assertion criteria provided clinical testing The BRCA1 p.Asp369del variant is an in-frame deletion resulting in the removal of an aspartic acid (Asp) residue at codon 369. The variant was identified in at least 11 of 116044 proband chromosomes (frequency: 0.0001) from individuals or families with breast cancer, and was not identified in 360 control chromosomes from healthy individuals (Borg 2010, Chenevix-Trench 2006 16489001, Couch 1996, Judkins 2005); however, an insufficient number of controls were included in these studies to determine the frequency of this variant in the general population. The variant is listed in dbSNP (ID: rs80358326) ?With untested allele?; however, no frequency information was available for the variant. The variant was also identified in HGMD, LOVD, and the BIC database (2X with unknown clinical importance), and the ClinVar database (with one ?uncertain significance? classification from BIC, and an unclassified submission from Invitae). Judkins (2005) identified this variant in trans with a known deleterious BRCA1 mutation (5385insC), increasing the likelihood that the p.Asp369del variant does not have clinical significance. A study by Chenevix-Trench (2006) demonstrated loss of the variant allele in tumours, suggesting that this variant is neutral. In addition, three multifactorial probability based models predict this to be a neutral variant (Chenevix-Trench 2006, Easton 2007, Lindor 2012). In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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.