Submissions for variant NM_000051.4(ATM):c.8240dup (p.Arg2748fs)

dbSNP: rs1591199097

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV001027315	SCV001189854	pathogenic	Hereditary cancer-predisposing syndrome	2022-05-31	criteria provided, single submitter	clinical testing	The c.8240dupA pathogenic mutation, located in coding exon 55 of the ATM gene, results from a duplication of A at nucleotide position 8240, causing a translational frameshift with a predicted alternate stop codon (p.R2748Efs*9). 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001049654	SCV001213719	pathogenic	Ataxia-telangiectasia syndrome	2024-08-27	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg2748Glufs*9) 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: 827530). For these reasons, this variant has been classified as Pathogenic.
Color Diagnostics, LLC DBA Color Health	RCV001027315	SCV001353973	pathogenic	Hereditary cancer-predisposing syndrome	2019-07-17	criteria provided, single submitter	clinical testing	This variant inserts one nucleotide in exon 56 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. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant 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). Loss of ATM function is a known mechanism of disease. Based on available evidence, this variant is classified as Pathogenic.
Baylor Genetics	RCV003467697	SCV004212237	pathogenic	Familial cancer of breast	2022-08-15	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003467697	SCV004932585	pathogenic	Familial cancer of breast	2024-02-02	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.