Submissions for variant NM_000051.4(ATM):c.3756_3757dup (p.Lys1253fs)

dbSNP: rs1555093289

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000540346	SCV000622455	pathogenic	Ataxia-telangiectasia syndrome	2023-10-03	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Lys1253Ilefs*4) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 453492). For these reasons, this variant has been classified as Pathogenic.
Color Diagnostics, LLC DBA Color Health	RCV000771669	SCV000904293	pathogenic	Hereditary cancer-predisposing syndrome	2020-01-15	criteria provided, single submitter	clinical testing	This variant inserts 2 nucleotides in exon 26 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. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of ATM function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Ambry Genetics	RCV000771669	SCV001182626	pathogenic	Hereditary cancer-predisposing syndrome	2022-11-04	criteria provided, single submitter	clinical testing	The c.3756_3757dupTA pathogenic mutation, located in coding exon 25 of the ATM gene, results from a duplication of TA at nucleotide position 3756, causing a translational frameshift with a predicted alternate stop codon (p.K1253Ifs*4). 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.
Baylor Genetics	RCV003470668	SCV004212174	likely pathogenic	Familial cancer of breast	2022-11-09	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003470668	SCV004932775	pathogenic	Familial cancer of breast	2024-01-23	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.