ClinVar Miner

Submissions for variant NM_001330368.2(C11orf65):c.641-38278dup (rs753961188)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000486055 SCV000569631 pathogenic not provided 2019-01-09 criteria provided, single submitter clinical testing This duplication of one nucleotide in ATM is denoted c.8655dupT at the cDNA level and p.Val2886CysfsX10 (V2886CfsX10) at the protein level. The normal sequence, with the base that is duplicated in brackets, is AACT[dupT]GTAC. The duplication causes a frameshift which changes a Valine to a Cysteine at codon 2886, and creates a premature stop codon at position 10 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. ATM c.8655dupT, also described as c.8653_8654insT using alternate nomenclature, has been reported in the compound heterozygous state with an ATM nonsense variant in a child with clinical features of Ataxia-telangiectasia (Barbaro 2017). Based on currently available evidence, we consider this to be a pathogenic variant.
Ambry Genetics RCV000569773 SCV000672647 pathogenic Hereditary cancer-predisposing syndrome 2018-06-12 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Color RCV000569773 SCV000682508 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
Invitae RCV000690610 SCV000818306 pathogenic Ataxia-telangiectasia syndrome 2019-04-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Val2886Cysfs*10) in the ATM gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs753961188, ExAC 0.008%). This variant has been observed on the opposite chromosome (in trans) from other pathogenic variant in an individual affected with ataxia-telangiectasia (PMID: 27873105). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. This variant is also known as c.8653_8654insT in the literature. ClinVar contains an entry for this variant (Variation ID: 420694). Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000690610 SCV001163275 pathogenic Ataxia-telangiectasia syndrome criteria provided, single submitter clinical testing

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