Submissions for variant NM_000051.4(ATM):c.4777-10dup

dbSNP: rs1398289633

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001704618	SCV000569226	likely benign	not provided	2021-04-24	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001184313	SCV001350263	likely benign	Hereditary cancer-predisposing syndrome	2018-10-26	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000480799	SCV001623221	uncertain significance	not specified	2021-05-03	criteria provided, single submitter	clinical testing	Variant summary: ATM c.4777-10dupT 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. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 251160 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.4777-10dupT has been reported in the literature in individuals affected with breast cancer (Bernstein_2010). This report does not provide unequivocal conclusions about association of the variant with breast cancer or Ataxia-Telangiectasia. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002056771	SCV002342433	likely benign	Ataxia-telangiectasia syndrome	2023-09-12	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV004591422	SCV005085502	likely benign	Familial cancer of breast	2024-05-21	criteria provided, single submitter	clinical testing	This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing.