ClinVar Miner

Submissions for variant NM_152783.5(D2HGDH):c.1039G>A (p.Ala347Thr)

gnomAD frequency: 0.00025  dbSNP: rs142624021
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001035164 SCV001198479 uncertain significance D-2-hydroxyglutaric aciduria 1 2022-10-13 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 347 of the D2HGDH protein (p.Ala347Thr). This variant is present in population databases (rs142624021, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with D2HGDH-related conditions. ClinVar contains an entry for this variant (Variation ID: 834472). 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 not expected to disrupt D2HGDH protein function. 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.
Baylor Genetics RCV001035164 SCV001526226 uncertain significance D-2-hydroxyglutaric aciduria 1 2018-11-16 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Ambry Genetics RCV002552082 SCV003680895 uncertain significance Inborn genetic diseases 2021-05-25 criteria provided, single submitter clinical testing The c.1039G>A (p.A347T) alteration is located in exon 8 (coding exon 7) of the D2HGDH gene. This alteration results from a G to A substitution at nucleotide position 1039, causing the alanine (A) at amino acid position 347 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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