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NM_020631.6(PLEKHG5):c.431G>T (p.Arg144Leu) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Sep 24, 2021
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:
RCV002034654.2

Allele description

NM_020631.6(PLEKHG5):c.431G>T (p.Arg144Leu)

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.431G>T (p.Arg144Leu)
HGVS:
  • NC_000001.11:g.6474459C>A
  • NG_007978.1:g.50551G>T
  • NG_089078.1:g.196C>A
  • NM_001042663.3:c.542G>T
  • NM_001042664.2:c.431G>T
  • NM_001042665.2:c.431G>T
  • NM_001265592.2:c.542G>T
  • NM_001265593.2:c.638G>T
  • NM_001265594.3:c.431G>T
  • NM_020631.6:c.431G>TMANE SELECT
  • NM_198681.4:c.431G>T
  • NP_001036128.2:p.Arg181Leu
  • NP_001036129.1:p.Arg144Leu
  • NP_001036129.1:p.Arg144Leu
  • NP_001036130.1:p.Arg144Leu
  • NP_001036130.1:p.Arg144Leu
  • NP_001252521.2:p.Arg181Leu
  • NP_001252522.1:p.Arg213Leu
  • NP_001252522.1:p.Arg213Leu
  • NP_001252523.1:p.Arg144Leu
  • NP_001252523.1:p.Arg144Leu
  • NP_065682.2:p.Arg144Leu
  • NP_065682.2:p.Arg144Leu
  • NP_941374.3:p.Arg144Leu
  • LRG_262t1:c.431G>T
  • LRG_262:g.50551G>T
  • LRG_262p1:p.Arg144Leu
  • NC_000001.10:g.6534519C>A
  • NM_001042664.1:c.431G>T
  • NM_001042665.1:c.431G>T
  • NM_001265593.1:c.638G>T
  • NM_001265594.2:c.431G>T
  • NM_020631.3:c.431G>T
Protein change:
R144L
Links:
dbSNP: rs150152888
NCBI 1000 Genomes Browser:
rs150152888
Molecular consequence:
  • NM_001042663.3:c.542G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001042664.2:c.431G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001042665.2:c.431G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001265592.2:c.542G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001265593.2:c.638G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001265594.3:c.431G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020631.6:c.431G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198681.4:c.431G>T - 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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002313725Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Sep 24, 2021) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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 Invitae, SCV002313725.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces arginine with leucine at codon 144 of the PLEKHG5 protein (p.Arg144Leu). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and leucine. This variant is not present in population databases (ExAC 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jan 26, 2024