Submissions for variant NM_153252.5(BRWD3):c.568C>T (p.Arg190Ter)

dbSNP: rs1057518650

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	RCV000415462	SCV004046190	pathogenic	Intellectual disability, X-linked 93		criteria provided, single submitter	clinical testing	This nonsense variant found in exon 7 of 41 is predicted to result in loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay (NMD). This variant has been previously reported in individuals with BRWD3-related syndromic X-linked intellectual disability (PMID: 27959697, 28475857, 31714006). In one individual, the c.568C>T (p.Arg190Ter) variant was inherited from a reportedly unaffected mother, whereas in another individual it was de novo together with another de novo variant in a different gene (CHD8). The c.568C>T (p.Arg190Ter) variant is absent from the gnomAD population database and thus is presumed to be rare. Analysis of the parental samples was negative for the variant, indicating this variant likely occurred as a de novo event. Based on the available evidence, the c.568C>T (p.Arg190Ter) variant is classified as Pathogenic.
Baylor Genetics	RCV000415462	SCV000328709	pathogenic	Intellectual disability, X-linked 93	2015-02-17	no assertion criteria provided	clinical testing	Our laboratory reported dual molecular diagnoses in BRWD3 (NM_153252.3, c.568C>T) and CHD8 (NM_001170629.1, c.2434C>T) in one individual with reported features of global developmental delay, autism, macrocephaly, mild chiari malformation, regression in speech development, and dysmorphic craniofacial features.