ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.8446A>C (p.Lys2816Gln)

dbSNP: rs1555138041
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000569004 SCV000665491 uncertain significance Hereditary cancer-predisposing syndrome 2016-03-01 criteria provided, single submitter clinical testing The p.K2816Q variant (also known as c.8446A>C), located in coding exon 57 of the ATM gene, results from an A to C substitution at nucleotide position 8446. The lysine at codon 2816 is replaced by glutamine, an amino acid with similar 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 6498 samples (12996 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, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001865740 SCV002145446 uncertain significance Ataxia-telangiectasia syndrome 2021-08-02 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamine at codon 2816 of the ATM protein (p.Lys2816Gln). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 481223). This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is not present in population databases (ExAC no frequency).

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