ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.2578G>A (p.Asp860Asn) (rs587779825)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000580576 SCV000682063 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-11 criteria provided, single submitter clinical testing
GeneDx RCV000115159 SCV000149068 uncertain significance not provided 2014-02-06 criteria provided, single submitter clinical testing This variant is denoted ATM c.2578G>A at the cDNA level, p.Asp860Asn (D860N) at the protein level, and results in the change of an Aspartic Acid to an Asparagine (GAT>AAT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Asp860Asn was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant is a semi-conservative substitution in which a negative polar amino acid is replaced with a neutral polar one, altering a position that is well conserved throughout evolution and is not located in a known functional domain. In silico analyses are inconsistent with regard to the effect this variant may have on protein structure and function. Based on the currently available information, we consider ATM Asp860Asn to be a variant of uncertain significance.
Invitae RCV000534079 SCV000622340 uncertain significance Ataxia-telangiectasia syndrome 2017-10-18 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 860 of the ATM protein (p.Asp860Asn). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs587779825, ExAC 0.02%). This variant has not been reported in the literature in individuals with an ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 127354). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, this variant has uncertain impact on ATM function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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