ClinVar Miner

Submissions for variant NM_018051.5(DYNC2I1):c.2305G>A (p.Glu769Lys)

gnomAD frequency: 0.00004  dbSNP: rs193204571
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002230998 SCV002508421 uncertain significance Short-rib thoracic dysplasia 8 with or without polydactyly 2021-08-28 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 769 of the WDR60 protein (p.Glu769Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs193204571, ExAC 0.04%). This variant has been observed in individual(s) with short-rib thoracic dysplasia (PMID: 29068549, Invitae). ClinVar contains an entry for this variant (Variation ID: 446627). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Center for Personalized Medicine, Children's Hospital Los Angeles RCV003156100 SCV003845338 likely pathogenic See cases 2022-12-21 criteria provided, single submitter clinical testing
Dan Cohn Lab, University Of California Los Angeles RCV000516105 SCV000612033 pathogenic Jeune thoracic dystrophy 2017-06-01 no assertion criteria provided research
Dan Cohn Lab, University Of California Los Angeles RCV001291411 SCV000612034 pathogenic Asphyxiating thoracic dystrophy 3 2017-06-01 no assertion criteria provided research
University of Washington Center for Mendelian Genomics, University of Washington RCV000516105 SCV001479910 likely pathogenic Jeune thoracic dystrophy no assertion criteria provided research
University of Washington Center for Mendelian Genomics, University of Washington RCV001291411 SCV001479911 likely pathogenic Asphyxiating thoracic dystrophy 3 no assertion criteria provided research
PreventionGenetics, part of Exact Sciences RCV003915443 SCV004738001 likely pathogenic DYNC2I1-related disorder 2023-12-18 no assertion criteria provided clinical testing The DYNC2I1 c.2305G>A variant is predicted to result in the amino acid substitution p.Glu769Lys. This variant has been reported in the homozygous and compound heterozygous state in two individuals affected with DYNC2I1-related disease (Table S2 ISDR Case # R04-477 and R91-028 in Zhang et al. 2018. PubMed ID: 29068549). At PreventionGenetics, we have observed this variant in the homozygous state in two affected patients. This variant is interpreted as pathogenic or likely pathogenic in the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/variation/446627/). This variant is reported in 0.029% of alleles in individuals of Latino descent in gnomAD. Based on the available evidence, we classify this variant as likely pathogenic.

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