Submissions for variant NM_000051.4(ATM):c.7516-9dup

dbSNP: rs573494809

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001537832	SCV000564659	likely benign	not provided	2023-07-10	criteria provided, single submitter	clinical testing	See Variant Classification Assertion Criteria.
Color Diagnostics, LLC DBA Color Health	RCV000580746	SCV000682421	likely benign	Hereditary cancer-predisposing syndrome	2015-04-27	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000486956	SCV001363784	benign	not specified	2019-11-08	criteria provided, single submitter	clinical testing	Variant summary: ATM c.7516-9dupT alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00035 in 228758 control chromosomes, predominantly at a frequency of 0.0017 within the East Asian subpopulation in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 2 fold of the estimated maximal expected allele frequency for a pathogenic variant in ATM causing Breast Cancer phenotype (0.001), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. To our knowledge, no occurrence of c.7516-9dupT in individuals affected with Breast Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign.
Invitae	RCV001516817	SCV001725168	benign	Ataxia-telangiectasia syndrome	2024-01-30	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000486956	SCV002760696	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003150232	SCV003837851	likely benign	Breast and/or ovarian cancer	2022-11-08	criteria provided, single submitter	clinical testing