NM_020631.6(PLEKHG5):c.1705G>A (p.Asp569Asn) AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Jun 30, 2020)
Review status:1 star out of maximum of 4 stars
criteria provided, single submitter

Help

Based on:: 1 submission [Details]
Record status:: current
Accession:: RCV000525392.6

Allele description [Variation Report for NM_020631.6(PLEKHG5):c.1705G>A (p.Asp569Asn)]

NM_020631.6(PLEKHG5):c.1705G>A (p.Asp569Asn)

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.1705G>A (p.Asp569Asn)

HGVS:

NC_000001.11:g.6470331C>T
NG_007978.1:g.54679G>A
NG_029910.1:g.865G>A
NM_001042663.3:c.1816G>A
NM_001042664.1:c.1705G>A
NM_001042665.1:c.1705G>A
NM_001265592.2:c.1816G>A
NM_001265593.1:c.1912G>A
NM_001265594.2:c.1705G>A
NM_020631.6:c.1705G>AMANE SELECT
NM_198681.4:c.1705G>A
NP_001036128.2:p.Asp606Asn
NP_001036129.1:p.Asp569Asn
NP_001036130.1:p.Asp569Asn
NP_001252521.2:p.Asp606Asn
NP_001252522.1:p.Asp638Asn
NP_001252523.1:p.Asp569Asn
NP_065682.2:p.Asp569Asn
NP_941374.3:p.Asp569Asn
LRG_262:g.54679G>A
NC_000001.10:g.6530391C>T
NM_020631.4:c.1705G>A

Protein change:

D569N

Links:

dbSNP: rs200641225

NCBI 1000 Genomes Browser:

rs200641225

Molecular consequence:

NM_001042663.3:c.1816G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001042664.1:c.1705G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001042665.1:c.1705G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001265592.2:c.1816G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001265593.1:c.1912G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001265594.2:c.1705G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_020631.6:c.1705G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_198681.4:c.1705G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Distal spinal muscular atrophy, autosomal recessive 4 (DSMA4)
Identifiers:: MONDO: MONDO:0012608; MedGen: C1970211; Orphanet: 206580; OMIM: 611067

Name:: Charcot-Marie-Tooth disease, recessive intermediate c (CMTRIC)
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
SCV000646007	Invitae	criteria provided, single submitter Invitae Variant Classification Sherloc (09022015)	Uncertain significance (Jun 30, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26392352, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000646007

Invitae

criteria provided, single submitter

Invitae Variant Classification Sherloc (09022015)

Uncertain significance
(Jun 30, 2020)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

Help

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

Application of targeted multi-gene panel testing for the diagnosis of inherited peripheral neuropathy provides a high diagnostic yield with unexpected phenotype-genotype variability.

Antoniadi T, Buxton C, Dennis G, Forrester N, Smith D, Lunt P, Burton-Jones S.

BMC Med Genet. 2015 Sep 21;16:84. doi: 10.1186/s12881-015-0224-8.

PubMed [citation]

PMID:: 26392352
PMCID:: PMC4578331

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000646007.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces aspartic acid with asparagine at codon 569 of the PLEKHG5 protein (p.Asp569Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs200641225, ExAC 0.06%). This variant has been reported in an individual affected with inherited peripheral neuropathy (PMID: 26392352). ClinVar contains an entry for this variant (Variation ID: 378377). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Tolerated; PolyPhen-2: Possibly Damaging; 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.

#	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: Nov 27, 2021

ClinVar

Relating variation to medicine