Submissions for variant NM_004840.3(ARHGEF6):c.685G>A (p.Val229Ile)

gnomAD frequency: 0.00146  dbSNP: rs75329154

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000192797	SCV000246485	likely benign	not specified	2015-04-20	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000263759	SCV000481792	likely benign	Non-syndromic X-linked intellectual disability	2016-06-14	criteria provided, single submitter	clinical testing
Invitae	RCV000877163	SCV001019855	likely benign	not provided	2018-03-30	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002362998	SCV002666052	uncertain significance	Inborn genetic diseases	2014-08-01	criteria provided, single submitter	clinical testing	The p.V229I variant (also known as c.685G>A), located in coding exon 6 of the ARHGEF6 gene, results from a G to A substitution at nucleotide position 685. The valine at codon 229 is replaced by isoleucine, an amino acid with highly similar properties. This variant was previously reported in the SNPDatabase as rs75329154. Based on data from the 1000 Genomes Project, the A allele has an overall frequency of approximately 0% (0/503) total male alleles studied.. Based on data from the NHLBI Exome Sequencing Project (ESP), the A allele has an overall frequency of approximately 0.08% (2/2443) total male alleles studied, having been observed in 0.18% (1/571) African American male alleles and 0.05% (1/1872) European American male alleles. This amino acid position is not conserved on species alignment. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
PreventionGenetics, part of Exact Sciences	RCV003927762	SCV004737899	likely benign	ARHGEF6-related condition	2019-10-17	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).
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000877163	SCV001797783	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000877163	SCV001963761	likely benign	not provided		no assertion criteria provided	clinical testing