Submissions for variant NM_000051.4(ATM):c.5762+1G>T

dbSNP: rs869312756

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
University of Washington Department of Laboratory Medicine, University of Washington	RCV000210115	SCV000266018	likely pathogenic	Hereditary cancer-predisposing syndrome	2015-11-20	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000210115	SCV000278229	pathogenic	Hereditary cancer-predisposing syndrome	2023-01-25	criteria provided, single submitter	clinical testing	The c.5762+1G>T pathogenic mutation results from a G to T substitution one nucleotide after coding exon 37 of the ATM gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Invitae	RCV000229503	SCV000282996	pathogenic	Ataxia-telangiectasia syndrome	2023-10-12	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 38 of the ATM gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with ovarian cancer (PMID: 26845104). ClinVar contains an entry for this variant (Variation ID: 224519). Studies have shown that disruption of this splice site results in skipping of exon 38 and introduces a premature termination codon (Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic.
Counsyl	RCV000229503	SCV000799105	likely pathogenic	Ataxia-telangiectasia syndrome	2018-04-11	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000210115	SCV001350787	likely pathogenic	Hereditary cancer-predisposing syndrome	2022-12-05	criteria provided, single submitter	clinical testing	This variant causes a G to T nucleotide substitution at the +1 position of intron 38 of the ATM gene. Splice site prediction tools predict that this variant may have a significant impact on RNA splicing. External laboratory's RNA studies have reported that this variant results in abnormal splicing (ClinVar SCV000278229.6). This variant has been reported in an individual affected with ovarian cancer (PMID: 26845104). 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 Likely Pathogenic.
Baylor Genetics	RCV003468971	SCV004212244	likely pathogenic	Familial cancer of breast	2022-07-07	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003468971	SCV004931263	likely pathogenic	Familial cancer of breast	2024-01-25	criteria provided, single submitter	clinical testing	This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function.