Submissions for variant NM_000051.4(ATM):c.4844del (p.Lys1615fs)

dbSNP: rs1555101791

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000572158	SCV000660628	pathogenic	Hereditary cancer-predisposing syndrome	2024-04-26	criteria provided, single submitter	clinical testing	The c.4844delA pathogenic mutation, located in coding exon 31 of the ATM gene, results from a deletion of one nucleotide at nucleotide position 4844, causing a translational frameshift with a predicted alternate stop codon (p.K1615Rfs*18). This mutation has been reported in multiple individuals with ataxia-telangiectasia (A-T) (Magliozzi M et al. Dis. Markers. 2006;22:257-64; Mohammadinejad P et al. J Immunoassay Immunochem. 2015;36:16-26). Of note, this alteration is also designated as 4842delA in published literature. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, 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	RCV000823667	SCV000964535	pathogenic	Ataxia-telangiectasia syndrome	2024-11-12	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Lys1615Argfs*18) 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 premature translational stop signal has been observed in individual(s) with ataxia-telangiectasia (PMID: 17124347, 24568663). This variant is also known as 4842delA. ClinVar contains an entry for this variant (Variation ID: 478996). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000823667	SCV001338154	pathogenic	Ataxia-telangiectasia syndrome	2020-02-14	criteria provided, single submitter	clinical testing	Variant summary: ATM c.4844delA (p.Lys1615ArgfsX18) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251350 control chromosomes (gnomAD). c.4844delA has been reported in the literature in individuals affected with Ataxia-Telangiectasia (Magliozzi_2006, Mohammadinejad_2015). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Revvity Omics, Revvity	RCV000823667	SCV002020100	pathogenic	Ataxia-telangiectasia syndrome	2019-06-04	criteria provided, single submitter	clinical testing