Submissions for variant NM_000051.4(ATM):c.1905C>T (p.His635=)

gnomAD frequency: 0.00003  dbSNP: rs1020808836

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000478597	SCV000570851	uncertain significance	not provided	2016-06-30	criteria provided, single submitter	clinical testing	This variant is denoted ATM c.1905C>T at the DNA level. This variant is silent at the coding level, preserving a Histidine at codon 635. This variant has not, to our knowledge, been published in the literature as being pathogenic or benign. In silico splicing models are uninformative, therefore, in the absence of RNA or functional studies, the actual effect of this variant is unknown. ATM c.1905C>T was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.The nucleotide which is altered, a cytosine (C) at base 1905, is not conserved. Based on currently available information, it is unclear whether ATM c.1905C>T is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics	RCV000575131	SCV000660769	likely benign	Hereditary cancer-predisposing syndrome	2017-04-13	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Color Diagnostics, LLC DBA Color Health	RCV000575131	SCV001349666	likely benign	Hereditary cancer-predisposing syndrome	2019-04-03	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001475097	SCV001679284	likely benign	Ataxia-telangiectasia syndrome	2023-11-24	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002307518	SCV002600332	likely benign	not specified	2022-10-07	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV004591427	SCV005084531	benign	Familial cancer of breast	2024-05-02	criteria provided, single submitter	clinical testing	This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.