Submissions for variant NM_000051.4(ATM):c.3153+5G>C

dbSNP: rs1591608756

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001524858	SCV001734824	uncertain significance	Hereditary cancer-predisposing syndrome	2020-12-09	criteria provided, single submitter	clinical testing	This variant causes a G to C nucleotide substitution at the +5 position of intron 21 of the ATM gene. Splice site prediction tools predict that this variant may have a significant impact on RNA splicing, however, this prediction has not been confirmed in published RNA studies. 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). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV001524858	SCV005037660	likely pathogenic	Hereditary cancer-predisposing syndrome	2024-01-05	criteria provided, single submitter	clinical testing	The c.3153+5G>C intronic variant results from a G to C substitution 5 nucleotides after coding exon 20 in the ATM gene. This nucleotide position is well 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 majority of available evidence to date, this variant is likely to be pathogenic.