ClinVar Miner

Submissions for variant NM_006796.3(AFG3L2):c.1219G>A (p.Asp407Asn)

dbSNP: rs2143171648
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001733428 SCV001983784 likely pathogenic not provided 2025-03-06 criteria provided, single submitter clinical testing In a preprint by Ferrer et al. (2023), the variant was reported as de novo in a patient with global developmental delay, failure to thrive, seizures, thinning of the optic chiasm, and mild atrophy of the optic nerves. Ferrer A et al. https://doi.org/10.21203/rs.3.rs-3146571/v1; 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; This variant is associated with the following publications: (PMID: 35982159, 37541188, Ferrer2023[Preprint], 33057194)
Labcorp Genetics (formerly Invitae), Labcorp RCV001733428 SCV003323743 pathogenic not provided 2022-12-29 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt AFG3L2 protein function. ClinVar contains an entry for this variant (Variation ID: 1301415). This missense change has been observed in individual(s) with clinical features of autosomal dominant spinocerebellar ataxia (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 407 of the AFG3L2 protein (p.Asp407Asn).
Revvity Omics, Revvity RCV001733428 SCV003820533 uncertain significance not provided 2021-09-03 criteria provided, single submitter clinical testing

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