Submissions for variant NM_000051.4(ATM):c.2466+2T>A

dbSNP: rs878853495

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000234163	SCV000282900	likely pathogenic	Ataxia-telangiectasia syndrome	2015-12-06	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature. Truncating variants in ATM are known to be pathogenic (PMID: 10817650, 19781682), and donor splice site variants are typically pathogenic (PMID: 16199547). In the absence of supporting functional or genetic data, this variant has been classified as Likely Pathogenic. This sequence change affects a donor splice site in intron 16. It is expected to disrupt mRNA splicing and likely results in an absent or disrupted protein product.
Neuberg Centre For Genomic Medicine, NCGM	RCV000234163	SCV004100554	likely pathogenic	Ataxia-telangiectasia syndrome		criteria provided, single submitter	clinical testing	The splice donor variant c.2466+2T>A in ATM (NM_000051.4) has been reported to ClinVar as Likely Pathogenic. It has not been reported previously in affected individuals. The c.2466+2T>A variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant affects an invariant splice site and hence is predicted to cause loss of function. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Likely Pathogenic.