ClinVar Miner

Submissions for variant NM_001377.3(DYNC2H1):c.9353+1G>A

gnomAD frequency: 0.00003  dbSNP: rs776407305
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000516136 SCV004296130 pathogenic Jeune thoracic dystrophy 2024-01-22 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 59 of the DYNC2H1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in DYNC2H1 are known to be pathogenic (PMID: 23339108, 32753734, 33755199). This variant is present in population databases (rs776407305, gnomAD 0.006%). Disruption of this splice site has been observed in individuals with DYNC2H1-related conditions (PMID: 23339108, 29068549). ClinVar contains an entry for this variant (Variation ID: 446543). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Dan Cohn Lab, University Of California Los Angeles RCV000516136 SCV000611919 pathogenic Jeune thoracic dystrophy 2017-06-01 no assertion criteria provided research
Dan Cohn Lab, University Of California Los Angeles RCV001291164 SCV000611967 pathogenic Asphyxiating thoracic dystrophy 3 2017-06-01 no assertion criteria provided research
University of Washington Center for Mendelian Genomics, University of Washington RCV001291164 SCV001479556 likely pathogenic Asphyxiating thoracic dystrophy 3 no assertion criteria provided research
University of Washington Center for Mendelian Genomics, University of Washington RCV000516136 SCV001479874 likely pathogenic Jeune thoracic dystrophy no assertion criteria provided research
PreventionGenetics, part of Exact Sciences RCV004742473 SCV005346938 likely pathogenic DYNC2H1-related disorder 2024-05-28 no assertion criteria provided clinical testing The DYNC2H1 c.9353+1G>A variant is predicted to disrupt the GT donor site and interfere with normal splicing. This variant was reported in a fetus with asphyxiating thoracic dystrophy (Fetus F3, Baujat et al. 2013. PubMed ID: 23339108), and in the compound heterozygous state in a patient with asphyxiating thoracic dystrophy (Patient R00-294A in Table S2, Zhang et al. 2017. PubMed ID: 29068549). This variant was also found in two other patients reported in Zhang et al., however, phase was not indicated or additional variants were also found (Patient R08-307 in Table S2 and R02-109 in Table S3, Zhang et al. 2017. PubMed ID: 29068549). This variant is reported in 0.0062% of alleles in individuals of Latino descent in gnomAD. Variants that disrupt the consensus splice donor site in DYNC2H1 are expected to be pathogenic. This variant is interpreted as likely pathogenic.

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