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

This record was updated by the submitter. Please see the current version.

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:: RCV001319593.6

Allele description

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001510344	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 17, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 32816195, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001510344

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 17, 2023)

germline

clinical testing

PubMed (2)
[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

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 Invitae, SCV001510344.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical 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).

#	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 16, 2024

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