ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.2506G>A (p.Glu836Lys)

gnomAD frequency: 0.00001  dbSNP: rs141054982
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159698 SCV000209707 uncertain significance not provided 2015-01-26 criteria provided, single submitter clinical testing This variant is denoted ATM c.2506G>A at the cDNA level, p.Glu836Lys (E836K) at the protein level, and results in the change of a Glutamic Acid to a Lysine (GAA>AAA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Glu836Lys was not observed at a significant allele frequency in the NHLBI Exome Sequencing Project. Since Glutamic Acid and Lysine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. ATM Glu836Lys occurs at a position that is variable across species and is not located in a known functional domain. In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available information, it is unclear whether ATM Glu836Lys is pathogenic or benign. We consider it to be a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV000462079 SCV000547063 uncertain significance Ataxia-telangiectasia syndrome 2023-09-21 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 181932). 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 output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The lysine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 836 of the ATM protein (p.Glu836Lys).
Ambry Genetics RCV002426786 SCV002741937 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-07 criteria provided, single submitter clinical testing The p.E836K variant (also known as c.2506G>A), located in coding exon 16 of the ATM gene, results from a G to A substitution at nucleotide position 2506. The glutamic acid at codon 836 is replaced by lysine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV002426786 SCV004360616 uncertain significance Hereditary cancer-predisposing syndrome 2023-11-06 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with lysine at codon 836 of the ATM protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with ATM-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Natera, Inc. RCV000462079 SCV002077907 uncertain significance Ataxia-telangiectasia syndrome 2021-02-22 no assertion criteria provided clinical testing

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