Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Equipe Genetique des Anomalies du Developpement, |
RCV000857315 | SCV000999917 | likely pathogenic | Intellectual disability, autosomal recessive 43 | 2019-06-03 | criteria provided, single submitter | research | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003987721 | SCV004804086 | uncertain significance | not specified | 2024-01-03 | criteria provided, single submitter | clinical testing | Variant summary: KIAA1033 c.1508A>G (p.His503Arg) results in a non-conservative amino acid change located in the WASH complex subunit 4, N-terminal domain (IPR028191) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00044 in 1613874 control chromosomes in the gnomAD v4 database, including 1 homozygote. c.1508A>G has been reported in the literature in at least one compound heterozygous individual affected with intellectual disability and/or multiple congenital anomalies (Bruel_2019). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 31231135, 35667337, 31953988, 34599609). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic and likely pathogenic. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| OMIM | RCV000857315 | SCV002549896 | pathogenic | Intellectual disability, autosomal recessive 43 | 2022-07-21 | no assertion criteria provided | literature only |