ClinVar Miner

Submissions for variant NM_145868.2(ANXA11):c.112G>A (p.Gly38Arg)

gnomAD frequency: 0.00005  dbSNP: rs142083484
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001860003 SCV002263274 pathogenic not provided 2024-11-08 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 38 of the ANXA11 protein (p.Gly38Arg). This variant is present in population databases (rs142083484, gnomAD 0.008%). This missense change has been observed in individuals with amyotrophic lateral sclerosis (PMID: 28469040, 29650794, 33087501, 33218681; internal data). ClinVar contains an entry for this variant (Variation ID: 488354). Algorithms developed to predict the effect of variants on gene product structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this missense change affects ANXA11 function (PMID: 28469040, 30109997, 33087501). For these reasons, this variant has been classified as Pathogenic.
Neurogenomics Lab, Neuroscience Institute, University Of Cape Town RCV003105971 SCV003761535 likely pathogenic Amyotrophic lateral sclerosis 2024-05-22 criteria provided, single submitter research PM2_supporting: the highest population allele frequency in gnomAD v4.0 is 0.00007705 (0.008%; 8/103830 alleles in European non-Finnish population) and in gnomAD v3.1.2 is 0.0004798 (0.048%; 1/2084 alleles in Other population) and the variant is absent from an internal database of 1412 alleles. PP3 met- multiple lines of computational evidence support a deleterious effect on the gene or gene product. PM1 met- variant is located in the N-terminal low complexity domain of ANXA11 near the calcyclin binding region and clusters with other pathogenic variants (p.P35A, p.P36R, p.D40G/p.D40Y). PS3_supporting- various functional studies provide evidence that this variant affects protein function (PMID 33087501, 30109997, 28469040). PS4_moderate- variant identified in 7 unrelated probands with consistent phenotype for disorder (PMID 35047667, 33218681, 33087501, 29650794, 28469040, clinical testing).
CeGaT Center for Human Genetics Tuebingen RCV001860003 SCV003916613 likely pathogenic not provided 2025-02-01 criteria provided, single submitter clinical testing ANXA11: PM1, PS3:Moderate, PS4:Moderate, PM2:Supporting
OMIM RCV000578149 SCV000679996 pathogenic Amyotrophic lateral sclerosis type 23 2018-01-30 no assertion criteria provided literature only
PreventionGenetics, part of Exact Sciences RCV003962641 SCV004779300 pathogenic ANXA11-related disorder 2024-02-09 no assertion criteria provided clinical testing The ANXA11 c.112G>A variant is predicted to result in the amino acid substitution p.Gly38Arg. This variant has been reported to be causative for amyotrophic lateral sclerosis (ALS, Smith et al. 2017. PubMed ID: 28469040; Müller et al. 2018. PubMed ID: 29650794; Teyssou et al. 2020. PubMed ID: 33218681). In vitro functional studies have shown the p.Gly38Arg variant leads to stress granule formation, and this supports its pathogenicity in ALS (Nahm et al. 2020. PubMed ID: 33087501). This variant is reported in 0.0077% of alleles in individuals of European (Non-Finnish) descent in gnomAD. This variant is interpreted as pathogenic.

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