ClinVar Miner

Submissions for variant NM_001377.3(DYNC2H1):c.6910G>A (p.Ala2304Thr)

dbSNP: rs747348765
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521573 SCV000617826 likely pathogenic not provided 2023-09-21 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 23456818, 29068549, 33875766, 29947050)
Clinical Genetics and Genomics, Karolinska University Hospital RCV000521573 SCV001449813 likely pathogenic not provided 2015-06-24 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000754936 SCV004291014 pathogenic Jeune thoracic dystrophy 2024-05-29 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 2304 of the DYNC2H1 protein (p.Ala2304Thr). This variant is present in population databases (rs747348765, gnomAD 0.07%). This missense change has been observed in individuals with clinical features of short-rib thoracic dysplasia with or without polydactyly (PMID: 23456818, 29068549). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 446539). 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 DYNC2H1 protein function with a negative predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV001291177 SCV005678324 likely pathogenic Asphyxiating thoracic dystrophy 3 2024-04-24 criteria provided, single submitter clinical testing
Dan Cohn Lab, University Of California Los Angeles RCV001291177 SCV000611914 pathogenic Asphyxiating thoracic dystrophy 3 2017-06-01 no assertion criteria provided research
Rare Disease Group, Clinical Genetics, Karolinska Institutet RCV000754936 SCV000788361 uncertain significance Jeune thoracic dystrophy 2018-05-01 flagged submission research
University of Washington Center for Mendelian Genomics, University of Washington RCV001291177 SCV001479595 likely pathogenic Asphyxiating thoracic dystrophy 3 no assertion criteria provided research
PreventionGenetics, part of Exact Sciences RCV003419889 SCV004117234 likely pathogenic DYNC2H1-related disorder 2024-02-02 no assertion criteria provided clinical testing The DYNC2H1 c.6910G>A variant is predicted to result in the amino acid substitution p.Ala2304Thr. This variant was reported in an individual with asphyxiating thoracic dystrophy (Table 2, Schmidts et al. 2013. PubMed ID: 23456818), and individuals with short-rib polydactyly syndrome (neonate in Table S2, Zhang et al. 2018. PubMed ID: 29068549; fetus in Table 2, Daum et al. 2019. PubMed ID: 29947050; Hammarsjö et al. 2021. PubMed ID: 33875766). This variant is reported in 0.070% of alleles in individuals of Ashkenazi Jewish descent in gnomAD. This variant is interpreted as likely pathogenic.

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