ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.6686T>A (p.Val2229Asp)

dbSNP: rs1555119144
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000579777 SCV000682359 uncertain significance Hereditary cancer-predisposing syndrome 2018-12-10 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000813695 SCV000954064 uncertain significance Ataxia-telangiectasia syndrome 2024-05-06 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 2229 of the ATM protein (p.Val2229Asp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 489578). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000579777 SCV002663530 uncertain significance Hereditary cancer-predisposing syndrome 2015-11-09 criteria provided, single submitter clinical testing The p.V2229D variant (also known as c.6686T>A), located in coding exon 45 of the ATM gene, results from a T to A substitution at nucleotide position 6686. The valine at codon 2229 is replaced by aspartic acid, an amino acid with highly dissimilar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6499 samples (12998 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 125000 alleles tested) in our clinical cohort. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be possibly damaging and deleterious by PolyPhen and SIFT in silico analyses, respectively. Since supporting evidence is limited at this time, the clinical significance of p.V2229D remains unclear.

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