NM_020631.6(PLEKHG5):c.1457_1482del (p.Gln486fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 16, 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:: RCV001957293.4

Allele description [Variation Report for NM_020631.6(PLEKHG5):c.1457_1482del (p.Gln486fs)]

NM_020631.6(PLEKHG5):c.1457_1482del (p.Gln486fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

1p36.31

Genomic location:

Preferred name:

NM_020631.6(PLEKHG5):c.1457_1482del (p.Gln486fs)

HGVS:

NC_000001.11:g.6470795_6470820del
NG_007978.1:g.54190_54215del
NG_029910.1:g.376_401del
NM_001042663.3:c.1568_1593del
NM_001042664.2:c.1457_1482del26
NM_001042665.2:c.1457_1482del26
NM_001265592.2:c.1568_1593del
NM_001265593.2:c.1664_1689del26
NM_001265594.3:c.1457_1482del26
NM_020631.6:c.1457_1482delMANE SELECT
NM_198681.4:c.1457_1482del
NP_001036128.2:p.Gln523fs
NP_001036129.1:p.Gln486Profs
NP_001036129.1:p.Gln486fs
NP_001036130.1:p.Gln486Profs
NP_001036130.1:p.Gln486fs
NP_001252521.2:p.Gln523fs
NP_001252522.1:p.Gln555Profs
NP_001252522.1:p.Gln555fs
NP_001252523.1:p.Gln486Profs
NP_001252523.1:p.Gln486fs
NP_065682.2:p.Gln486Profs
NP_065682.2:p.Gln486fs
NP_941374.3:p.Gln486fs
LRG_262t1:c.1457_1482del26
LRG_262:g.54190_54215del
LRG_262p1:p.Gln486Profs
NC_000001.10:g.6530855_6530880del
NM_001042664.1:c.1457_1482del
NM_001042665.1:c.1457_1482del
NM_001265593.1:c.1664_1689del
NM_001265594.2:c.1457_1482del
NM_020631.3:c.1457_1482del26

Protein change:

Q486fs

Links:

dbSNP: rs1266507622

NCBI 1000 Genomes Browser:

rs1266507622

Molecular consequence:

NM_001042663.3:c.1568_1593del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001042664.2:c.1457_1482del26 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001042665.2:c.1457_1482del26 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001265592.2:c.1568_1593del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001265593.2:c.1664_1689del26 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001265594.3:c.1457_1482del26 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_020631.6:c.1457_1482del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_198681.4:c.1457_1482del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV002207418	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 16, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17564964, 23777631, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002207418

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 16, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

The nuclear factor kappaB-activator gene PLEKHG5 is mutated in a form of autosomal recessive lower motor neuron disease with childhood onset.

Maystadt I, Rezsöhazy R, Barkats M, Duque S, Vannuffel P, Remacle S, Lambert B, Najimi M, Sokal E, Munnich A, Viollet L, Verellen-Dumoulin C.

Am J Hum Genet. 2007 Jul;81(1):67-76. Epub 2007 May 16.

PubMed [citation]

PMID:: 17564964
PMCID:: PMC1950913

PLEKHG5 deficiency leads to an intermediate form of autosomal-recessive Charcot-Marie-Tooth disease.

Azzedine H, Zavadakova P, Planté-Bordeneuve V, Vaz Pato M, Pinto N, Bartesaghi L, Zenker J, Poirot O, Bernard-Marissal N, Arnaud Gouttenoire E, Cartoni R, Title A, Venturini G, Médard JJ, Makowski E, Schöls L, Claeys KG, Stendel C, Roos A, Weis J, Dubourg O, Leal Loureiro J, et al.

Hum Mol Genet. 2013 Oct 15;22(20):4224-32. doi: 10.1093/hmg/ddt274. Epub 2013 Jun 17.

PubMed [citation]

PMID:: 23777631
PMCID:: PMC3983407

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002207418.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1424950). This variant has not been reported in the literature in individuals affected with PLEKHG5-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln486Profs*160) in the PLEKHG5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PLEKHG5 are known to be pathogenic (PMID: 17564964, 23777631).

#	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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