Submissions for variant NM_000051.4(ATM):c.2598T>G (p.Val866=)

gnomAD frequency: 0.00001  dbSNP: rs730881350

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000159699	SCV000209709	uncertain significance	not provided	2014-07-02	criteria provided, single submitter	clinical testing	This variant is denoted ATM c.2598T>G at the DNA level. Although the variant is silent at the coding level, preserving a Valine at codon 866, it is predicted to cause abnormal splicing. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM 2598T>G 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 thymine (T) at base 2598, is moderately conserved across species with guanine (G) being the naturally occurring amino acid in other mammals. Based on currently available information, it is unclear whether ATM 2598T>G is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics	RCV000562239	SCV000665252	likely benign	Hereditary cancer-predisposing syndrome	2018-03-09	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	RCV000562239	SCV000913902	likely benign	Hereditary cancer-predisposing syndrome	2018-06-26	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001078605	SCV001070380	likely benign	Ataxia-telangiectasia syndrome	2023-12-30	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001199919	SCV001370694	likely benign	not specified	2020-05-30	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV004589671	SCV005085139	benign	Familial cancer of breast	2024-05-09	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.