ClinVar Miner

Submissions for variant NM_198578.4(LRRK2):c.6428G>A (p.Arg2143His)

gnomAD frequency: 0.00009  dbSNP: rs201271001
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000032501 SCV001267600 uncertain significance Autosomal dominant Parkinson disease 8 2017-04-28 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.
Invitae RCV000032501 SCV003262944 uncertain significance Autosomal dominant Parkinson disease 8 2022-09-26 criteria provided, single submitter clinical testing 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. Experimental studies have shown that this missense change does not substantially affect LRRK2 function (PMID: 20642453). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 39227). This missense change has been observed in individual(s) with Parkinson disease (PMID: 18213618). This variant is present in population databases (rs201271001, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 2143 of the LRRK2 protein (p.Arg2143His).
GeneReviews RCV000032501 SCV000056164 not provided Autosomal dominant Parkinson disease 8 no assertion provided literature only

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