Submissions for variant NM_016023.5(OTUD6B):c.389C>A (p.Ala130Asp)

gnomAD frequency: 0.00116  dbSNP: rs143832637

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000883270	SCV001026563	likely benign	not provided	2018-11-15	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001193305	SCV001362055	uncertain significance	not specified	2019-11-12	criteria provided, single submitter	clinical testing	Variant summary: OTUD6B c.479C>A (p.Ala160Asp) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00035 in 226198 control chromosomes, predominantly at a frequency of 0.0045 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 4-fold of the estimated maximal expected allele frequency for a pathogenic variant in OTUD6B causing Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies phenotype (0.0011), 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.479C>A in individuals affected with Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies 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 VUS-possibly benign.
Baylor Genetics	RCV001335783	SCV001529017	uncertain significance	Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies	2018-04-11	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
GeneDx	RCV000883270	SCV001982755	uncertain significance	not provided	2024-10-16	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
PreventionGenetics, part of Exact Sciences	RCV003940471	SCV004753749	likely benign	OTUD6B-related disorder	2019-02-21	no assertion criteria provided	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).