Submissions for variant NM_000051.4(ATM):c.1483dup (p.Ile495fs)

dbSNP: rs2135324290

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001804540	SCV002053264	pathogenic	Hereditary cancer-predisposing syndrome	2021-03-16	criteria provided, single submitter	clinical testing	This variant inserts 1 nucleotide in exon 10 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. To our knowledge, 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). Loss of ATM function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002541409	SCV003199965	pathogenic	Ataxia-telangiectasia syndrome	2023-09-26	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 1332024). This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ile495Asnfs*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). For these reasons, this variant has been classified as Pathogenic.