Submissions for variant NM_000051.4(ATM):c.8419-7_8419-4del

dbSNP: rs730881306

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000159635	SCV000209624	uncertain significance	not provided	2014-09-08	criteria provided, single submitter	clinical testing	This variant is denoted ATM c.8419-(7_4)delTTTA or IVS57-(7_4)delTTTA and consists of a deletion of four nucleotides at the -4 to -7 position in intron 57 of the ATM gene. The normal sequence with the bases that are deleted in brackets is tcta[delTTTA]aagG. Multiple in silico models predict this variant to weaken or destroy the nearby natural acceptor site, and to possibly cause abnormal gene splicing. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. The nucleotides that are deleted are moderately conserved across species. Based on currently available information, it is unclear whether ATM c.8419-(7_4)delTTTA is pathogenic or benign. We consider it to be a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000628073	SCV000748962	likely benign	Ataxia-telangiectasia syndrome	2024-01-02	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000771941	SCV000904754	uncertain significance	Hereditary cancer-predisposing syndrome	2022-08-15	criteria provided, single submitter	clinical testing	This variant removes 4 nucleotides at the +4 to +7 positions in the intron 57 acceptor region of the ATM gene. Splice site prediction tools predict that this variant may have a significant impact on RNA splicing. To our knowledge, RNA analysis studies have not been reported 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.
Sema4, Sema4	RCV000771941	SCV002527296	uncertain significance	Hereditary cancer-predisposing syndrome	2022-02-02	criteria provided, single submitter	curation
Ambry Genetics	RCV000771941	SCV002675814	uncertain significance	Hereditary cancer-predisposing syndrome	2024-02-01	criteria provided, single submitter	clinical testing	The c.8419-7_8419-4delTTTA intronic variant, located in intron 56 of the ATM gene, results from a deletion of 4 nucleotides within intron 56 of the ATM gene. This nucleotide region is well conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive; however, direct evidence is insufficient at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Natera, Inc.	RCV000628073	SCV002079538	uncertain significance	Ataxia-telangiectasia syndrome	2020-09-29	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004739494	SCV005366686	uncertain significance	ATM-related disorder	2024-08-26	no assertion criteria provided	clinical testing	The ATM c.8419-7_8419-4delTTTA variant is predicted to result in an intronic deletion. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. This variant has conflicting interpretations regarding its pathogenicity in ClinVar, ranging from uncertain significance to likely benign (https://www.ncbi.nlm.nih.gov/clinvar/variation/181877/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.