ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.8480T>G (p.Phe2827Cys) (rs121434216)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000581067 SCV000682490 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-18 criteria provided, single submitter clinical testing
Invitae RCV000628126 SCV000749019 likely pathogenic Ataxia-telangiectasia syndrome 2018-12-11 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with cysteine at codon 2827 of the ATM protein (p.Phe2827Cys). The phenylalanine residue is highly conserved and there is a large physicochemical difference between phenylalanine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with a relatively mild form of ataxia-telangiectasia (PMID: 8755918). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 3022). Experimental studies have shown that this missense change results in reduced expression of the ATM protein and decreased ATM kinase activity in comparison with wild-type (PMID: 19431188, 25040471, 9000145). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000003158 SCV000023316 pathogenic Ataxia-telangiectasia variant 1996-08-01 no assertion criteria provided literature only

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