Submissions for variant NM_020631.6(PLEKHG5):c.307G>A (p.Val103Met)

gnomAD frequency: 0.00209  dbSNP: rs141032388

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000313379	SCV000358775	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.
Invitae	RCV001083174	SCV000646048	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
CeGaT Center for Human Genetics Tuebingen	RCV000761631	SCV000891801	uncertain significance	not provided	2022-08-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000761631	SCV001470950	uncertain significance	not provided	2023-10-09	criteria provided, single submitter	clinical testing	The PLEKHG5 c.307G>A; p.Val103Met variant (rs141032388), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 245660). This variant is found in the general population with an allele frequency of 0.19% (531/281480 alleles) in the Genome Aggregation Database. The valine at codon 103 is moderately conserved, and computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.426). Due to limited information, the clinical significance of this variant is uncertain at this time.
Ambry Genetics	RCV002319471	SCV002608815	likely benign	Inborn genetic diseases	2019-09-18	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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	RCV003955384	SCV004774390	likely benign	PLEKHG5-related condition	2021-02-03	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).