Submissions for variant NM_000051.4(ATM):c.2839-4T>C

dbSNP: rs1057522619

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001357612	SCV000528643	likely benign	not provided	2020-07-31	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000527197	SCV000622368	likely benign	Ataxia-telangiectasia syndrome	2023-11-25	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000574947	SCV000665263	likely benign	Hereditary cancer-predisposing syndrome	2019-10-23	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	RCV000574947	SCV000912155	uncertain significance	Hereditary cancer-predisposing syndrome	2022-08-08	criteria provided, single submitter	clinical testing	This variant causes a T>C nucleotide substitution at the -4 position of intron 18 of the ATM gene. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Myriad Genetics, Inc.	RCV004591234	SCV005082748	likely benign	Familial cancer of breast	2024-05-10	criteria provided, single submitter	clinical testing	This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing.
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001357612	SCV001553133	uncertain significance	not provided		no assertion criteria provided	clinical testing	The ATM c.2839-4T>C variant was not identified in the literature nor was it identified in the following databases: dbSNP, COGR, Cosmic, LOVD 3.0, and ATM-LOVD. The variant was identified in ClinVar (classified as likely benign by GeneDx and Invitae and classified as uncertain significance by Ambry Genetics). The variant was also not identified in the following control databases: the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The c.2839-4T>C variant is located in the 3' splice region but does not affect the invariant -1 or -2 positions. Positions -3 and -5 to -12 are also part of the splicing consensus sequence and variants involving these positions sometimes affect splicing; however, this variant is not located at any of these positions. Further, only 1 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predicts a greater than 10% difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.