ClinVar Miner

Submissions for variant NM_001377.3(DYNC2H1):c.6894-4G>A

gnomAD frequency: 0.00168  dbSNP: rs17100043
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001707785 SCV000721495 likely benign not provided 2020-09-11 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000862754 SCV001003302 benign Jeune thoracic dystrophy 2024-01-31 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003235308 SCV003934720 benign not specified 2023-05-10 criteria provided, single submitter clinical testing Variant summary: DYNC2H1 c.6894-4G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00037 in 247204 control chromosomes, predominantly at a frequency of 0.0049 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 2 fold of the estimated maximal expected allele frequency for a pathogenic variant in DYNC2H1 causing Short-rib thoracic dysplasia phenotype (0.0025), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.6894-4G>A in individuals affected with Short-rib thoracic dysplasia and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.

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