Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001253771 | SCV005040545 | likely pathogenic | Neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia | 2024-03-01 | criteria provided, single submitter | clinical testing | Variant summary: DOCK3 c.1038-2A>G is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a canonical 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The frequency data for this variant in gnomAD is considered unreliable, as metrics indicate poor data quality at this position. c.1038-2A>G has been reported in the literature in an individual affected with Neurodevelopmental Disorder With Impaired Intellectual Developmen and Hypotonia (Wiltrout_2019), and they were compound heterozygous with a pathogenic variant. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 30976111). ClinVar contains an entry for this variant (Variation ID: 599269). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| The Division of Genetics and Genomic Medicine, |
RCV001841880 | SCV000852082 | pathogenic | Global developmental delay; Hypotonia | 2017-03-31 | no assertion criteria provided | clinical testing | |
| OMIM | RCV001253771 | SCV001429644 | pathogenic | Neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia | 2020-08-12 | no assertion criteria provided | literature only |