ClinVar Miner

Submissions for variant NM_004304.5(ALK):c.2452G>A (p.Gly818Arg)

gnomAD frequency: 0.00003  dbSNP: rs777803249
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000706090 SCV000835122 uncertain significance Neuroblastoma, susceptibility to, 3 2024-06-10 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 818 of the ALK protein (p.Gly818Arg). This variant is present in population databases (rs777803249, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with ALK-related conditions. ClinVar contains an entry for this variant (Variation ID: 582105). 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.
Illumina Laboratory Services, Illumina RCV000706090 SCV001299495 uncertain significance Neuroblastoma, susceptibility to, 3 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
GeneDx RCV004760748 SCV005371200 uncertain significance not provided 2024-03-12 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 25714698)
Ambry Genetics RCV005338334 SCV006007585 uncertain significance Hereditary cancer-predisposing syndrome 2025-01-02 criteria provided, single submitter clinical testing The p.G818R variant (also known as c.2452G>A), located in coding exon 14 of the ALK gene, results from a G to A substitution at nucleotide position 2452. The glycine at codon 818 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.

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