NM_020631.6(PLEKHG5):c.1668C>G (p.Asp556Glu) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 18, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003011763.3

Allele description [Variation Report for NM_020631.6(PLEKHG5):c.1668C>G (p.Asp556Glu)]

NM_020631.6(PLEKHG5):c.1668C>G (p.Asp556Glu)

Gene:

PLEKHG5:pleckstrin homology and RhoGEF domain containing G5 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.31

Genomic location:

Preferred name:

NM_020631.6(PLEKHG5):c.1668C>G (p.Asp556Glu)

HGVS:

NC_000001.11:g.6470518G>C
NG_007978.1:g.54492C>G
NG_029910.1:g.678C>G
NM_001042663.3:c.1779C>G
NM_001042664.2:c.1668C>G
NM_001042665.2:c.1668C>G
NM_001265592.2:c.1779C>G
NM_001265593.2:c.1875C>G
NM_001265594.3:c.1668C>G
NM_020631.6:c.1668C>GMANE SELECT
NM_198681.4:c.1668C>G
NP_001036128.2:p.Asp593Glu
NP_001036129.1:p.Asp556Glu
NP_001036129.1:p.Asp556Glu
NP_001036130.1:p.Asp556Glu
NP_001036130.1:p.Asp556Glu
NP_001252521.2:p.Asp593Glu
NP_001252522.1:p.Asp625Glu
NP_001252522.1:p.Asp625Glu
NP_001252523.1:p.Asp556Glu
NP_001252523.1:p.Asp556Glu
NP_065682.2:p.Asp556Glu
NP_065682.2:p.Asp556Glu
NP_941374.3:p.Asp556Glu
LRG_262t1:c.1668C>G
LRG_262:g.54492C>G
LRG_262p1:p.Asp556Glu
NC_000001.10:g.6530578G>C
NM_001042664.1:c.1668C>G
NM_001042665.1:c.1668C>G
NM_001265593.1:c.1875C>G
NM_001265594.2:c.1668C>G
NM_020631.3:c.1668C>G

Protein change:

D556E

Molecular consequence:

NM_001042663.3:c.1779C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001042664.2:c.1668C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001042665.2:c.1668C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001265592.2:c.1779C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001265593.2:c.1875C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001265594.3:c.1668C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_020631.6:c.1668C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_198681.4:c.1668C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Neuronopathy, distal hereditary motor, autosomal recessive 4
Synonyms:: Distal spinal muscular atrophy, autosomal recessive 4; Autosomal recessive lower motor neuron disease with childhood onset; NEUROPATHY, DISTAL HEREDITARY MOTOR, AUTOSOMAL RECESSIVE 4
Identifiers:: MONDO: MONDO:0012608; MedGen: C1970211; Orphanet: 206580; OMIM: 611067

Name:: Charcot-Marie-Tooth disease recessive intermediate C
Synonyms:: CHARCOT-MARIE-TOOTH NEUROPATHY, RECESSIVE INTERMEDIATE C
Identifiers:: MONDO: MONDO:0014154; MedGen: C3809309; Orphanet: 369867; OMIM: 615376

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003305905	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 18, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003305905

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 18, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003305905.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 556 of the PLEKHG5 protein (p.Asp556Glu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PLEKHG5-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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