Submissions for variant NM_001376.5(DYNC1H1):c.5050-3C>T

gnomAD frequency: 0.00021  dbSNP: rs372462176

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000809818	SCV000949997	uncertain significance	Charcot-Marie-Tooth disease axonal type 2O	2024-01-06	criteria provided, single submitter	clinical testing	This sequence change falls in intron 24 of the DYNC1H1 gene. It does not directly change the encoded amino acid sequence of the DYNC1H1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs372462176, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with DYNC1H1-related conditions. ClinVar contains an entry for this variant (Variation ID: 653953). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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.
GeneDx	RCV001655605	SCV001871361	likely benign	not provided	2021-01-19	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002336662	SCV002641878	likely benign	Inborn genetic diseases	2021-01-08	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.