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NM_014846.4(WASHC5):c.3104G>A (p.Arg1035His) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Apr 17, 2023
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:
RCV001319593.7

Allele description [Variation Report for NM_014846.4(WASHC5):c.3104G>A (p.Arg1035His)]

NM_014846.4(WASHC5):c.3104G>A (p.Arg1035His)

Gene:
WASHC5:WASH complex subunit 5 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
8q24.13
Genomic location:
Preferred name:
NM_014846.4(WASHC5):c.3104G>A (p.Arg1035His)
HGVS:
  • NC_000008.11:g.125037314C>T
  • NG_012636.1:g.59506G>A
  • NM_001330609.2:c.2660G>A
  • NM_014846.4:c.3104G>AMANE SELECT
  • NP_001317538.1:p.Arg887His
  • NP_055661.3:p.Arg1035His
  • NC_000008.10:g.126049556C>T
  • NM_014846.3:c.3104G>A
Protein change:
R1035H
Links:
dbSNP: rs761500521
NCBI 1000 Genomes Browser:
rs761500521
Molecular consequence:
  • NM_001330609.2:c.2660G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_014846.4:c.3104G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary spastic paraplegia 8 (SPG8)
Synonyms:
SPASTIC PARAPLEGIA 8, AUTOSOMAL DOMINANT; Spastic paraplegia 8
Identifiers:
MONDO: MONDO:0011339; MedGen: C1863704; Orphanet: 100989; OMIM: 603563
Name:
Ritscher-Schinzel syndrome (RTSC1)
Synonyms:
Dandy-Walker like malformation with atrioventricular septal defect; Cranio-cerebello-cardiac dysplasia; 3C syndrome; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0019078; MedGen: C0796137; OMIM: PS220210

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001510344Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Apr 17, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Inherited Cerebellar Ataxias: 5-Year Experience of the Irish National Ataxia Clinic.

Bogdanova-Mihaylova P, Hebert J, Moran S, Murphy M, Ward D, Walsh RA, Murphy SM.

Cerebellum. 2021 Feb;20(1):54-61. doi: 10.1007/s12311-020-01180-0.

PubMed [citation]
PMID:
32816195

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, SCV001510344.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt WASHC5 protein function. ClinVar contains an entry for this variant (Variation ID: 410081). This missense change has been observed in individual(s) with WASHC5-related conditions (PMID: 32816195). This variant is present in population databases (rs761500521, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1035 of the WASHC5 protein (p.Arg1035His).

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

Last Updated: Nov 3, 2024