Submissions for variant NM_020631.6(PLEKHG5):c.88C>T (p.Arg30Cys)

gnomAD frequency: 0.00274  dbSNP: rs111400494

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000235739	SCV000292662	benign	not specified	2017-12-27	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.
Eurofins Ntd Llc (ga)	RCV000235739	SCV000333624	benign	not specified	2015-10-29	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000268718	SCV000358777	likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
CeGaT Center for Human Genetics Tuebingen	RCV000488190	SCV000574738	likely benign	not provided	2024-01-01	criteria provided, single submitter	clinical testing	PLEKHG5: BS2
Labcorp Genetics (formerly Invitae), Labcorp	RCV001080020	SCV000646071	likely benign	Neuronopathy, distal hereditary motor, autosomal recessive 4; Charcot-Marie-Tooth disease recessive intermediate C	2024-01-31	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000488190	SCV001157412	uncertain significance	not provided	2023-11-01	criteria provided, single submitter	clinical testing	The PLEKHG5 c.88C>T; p.Arg30Cys variant (rs111400494), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 245659). This variant is found in the non-Finnish European population with an allele frequency of 0.4% (503/128,500 alleles, including 2 homozygotes) in the Genome Aggregation Database. The arginine at codon 30 is moderately conserved, but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.225). Due to limited information, the clinical significance of the p.Arg30Cys variant is uncertain at this time.
Ambry Genetics	RCV002374387	SCV002685549	likely benign	Inborn genetic diseases	2020-06-18	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.
PreventionGenetics, part of Exact Sciences	RCV003939904	SCV004752551	benign	PLEKHG5-related disorder	2023-04-27	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).