Submissions for variant NM_000051.4(ATM):c.3820C>T (p.Gln1274Ter)

gnomAD frequency: 0.00001  dbSNP: rs1453429915

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001385735	SCV001585697	pathogenic	Ataxia-telangiectasia syndrome	2020-03-04	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals with ATM-related conditions. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln1274*) in the ATM gene. It is expected to result in an absent or disrupted protein product.
Neuberg Centre For Genomic Medicine, NCGM	RCV001385735	SCV004047927	uncertain significance	Ataxia-telangiectasia syndrome		criteria provided, single submitter	clinical testing	The stop gained variant c.3820C>T(p.Gln1274Ter) has been submitted to ClinVar as a Pathogenic, but no details are available for independent assessment. The c.3820C>T variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. This variant has been reported to the ClinVar database as Pathogenic. The nucleotide change c.3820C>T in ATM is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Likely Pathogenic.