Submissions for variant NM_020631.6(PLEKHG5):c.495G>A (p.Lys165=)

gnomAD frequency: 0.00183  dbSNP: rs150772386

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000335921	SCV000358770	benign	Neuronopathy, distal hereditary motor, autosomal recessive 4	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx	RCV000434281	SCV000517060	benign	not specified	2016-07-28	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000541394	SCV000646054	benign	Neuronopathy, distal hereditary motor, autosomal recessive 4; Charcot-Marie-Tooth disease recessive intermediate C	2025-01-29	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002338876	SCV002642668	likely benign	Inborn genetic diseases	2019-07-11	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Breakthrough Genomics, Breakthrough Genomics	RCV004714792	SCV005282322	benign	not provided		criteria provided, single submitter	not provided
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV004714792	SCV005877152	benign	not provided	2024-10-02	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003920211	SCV004729796	benign	PLEKHG5-related disorder	2019-07-19	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).