Submissions for variant NM_004947.5(DOCK3):c.5145+4C>T

gnomAD frequency: 0.00073  dbSNP: rs138743227

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001255572	SCV001432058	uncertain significance	not specified	2020-08-28	criteria provided, single submitter	clinical testing	Variant summary: DOCK3 c.5145+4C>T 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 0.00015 in 226710 control chromosomes (gnomAD). To our knowledge, no occurrence of c.5145+4C>T in individuals affected with Neurodevelopmental Disorder With Impaired Intellectual Development, Hypotonia, And Ataxia and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
PreventionGenetics, part of Exact Sciences	RCV003963159	SCV004779136	likely benign	DOCK3-related disorder	2019-08-29	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).