Submissions for variant NM_000051.4(ATM):c.15dup (p.Asn6Ter)

dbSNP: rs876660842

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000213282	SCV000278590	pathogenic	Hereditary cancer-predisposing syndrome	2023-03-13	criteria provided, single submitter	clinical testing	The c.15dupT pathogenic mutation, located in coding exon 1 of the ATM gene, results from a duplication of T at nucleotide position 15, causing a translational frameshift with a predicted alternate stop codon (p.N6*). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
GeneDx	RCV000485951	SCV000572144	pathogenic	not provided	2016-10-26	criteria provided, single submitter	clinical testing	This duplication of one nucleotide is denoted ATM c.15dupT at the cDNA level and p.Asn6Ter (N6X) at the protein level. The normal sequence, with the base that is duplicated in braces, is TACT[T]AATG. The duplication creates a nonsense variant, which changes an Asparagine to a premature stop codon. Although this variant has not been previously reported to our knowledge, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay, and is considered pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001047848	SCV001211830	pathogenic	Ataxia-telangiectasia syndrome	2020-06-09	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 234089). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Asn6*) in the ATM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic.
Color Diagnostics, LLC DBA Color Health	RCV000213282	SCV001349492	pathogenic	Hereditary cancer-predisposing syndrome	2019-09-16	criteria provided, single submitter	clinical testing	This variant inserts 1 nucleotide in exon 2 of the ATM gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. Splice site prediction tools suggest that this variant may not impact RNA splicing. 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 been identified in 1/251396 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of ATM function is a known mechanism of disease. Based on the available evidence, this variant is classified as Pathogenic.
Baylor Genetics	RCV003469099	SCV004207729	likely pathogenic	Familial cancer of breast	2023-08-22	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003469099	SCV004933496	pathogenic	Familial cancer of breast	2024-01-05	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.