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

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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000646007Invitaecriteria provided, single submitter
Uncertain significance
(Jun 30, 2020)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical 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.

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

Last Updated: Nov 27, 2021

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