NM_213655.5(WNK1):c.2650G>A (p.Val884Ile) AND multiple conditions

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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 27, 2024
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:: RCV001050993.5

Allele description

NM_213655.5(WNK1):c.2650G>A (p.Val884Ile)

Gene:

WNK1:WNK lysine deficient protein kinase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12p13.33

Genomic location:

Preferred name:

NM_213655.5(WNK1):c.2650G>A (p.Val884Ile)

HGVS:

NC_000012.12:g.868121G>A
NG_007984.3:g.120063G>A
NM_001184985.2:c.2395G>A
NM_014823.3:c.2140-3144G>A
NM_018979.4:c.2140-3144G>AMANE SELECT
NM_213655.5:c.2650G>A
NP_001171914.1:p.Val799Ile
NP_998820.3:p.Val884Ile
NP_998820.3:p.Val884Ile
LRG_247t1:c.2140-3144G>A
LRG_247t2:c.2650G>A
LRG_247:g.120063G>A
LRG_247p2:p.Val884Ile
NC_000012.11:g.977287G>A
NM_213655.4:c.2650G>A

Protein change:

V799I

Links:

dbSNP: rs764190549

NCBI 1000 Genomes Browser:

rs764190549

Molecular consequence:

NM_014823.3:c.2140-3144G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_018979.4:c.2140-3144G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001184985.2:c.2395G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_213655.5:c.2650G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Neuropathy, hereditary sensory and autonomic, type 2A (HSAN2A)
Synonyms:: ACROOSTEOLYSIS, GIACCAI TYPE; ACROOSTEOLYSIS, NEUROGENIC; HSAN IIA; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0024309; MedGen: C2752089; Orphanet: 970; OMIM: 201300

Name:: Pseudohypoaldosteronism type 2C (PHA2C)
Identifiers:: MONDO: MONDO:0013778; MedGen: C1840391; Orphanet: 757; OMIM: 614492

Recent activity

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Homo sapiens mucin 3A, cell surface associated (MUC3A), mRNA
Homo sapiens mucin 3A, cell surface associated (MUC3A), mRNA
gi|1519242548|ref|NM_005960.2|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001215126	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 27, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001215126

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 27, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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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

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, SCV001215126.5

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

Description

This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 884 of the WNK1 protein (p.Val884Ile). This variant is present in population databases (rs764190549, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with WNK1-related conditions. ClinVar contains an entry for this variant (Variation ID: 847450). 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 WNK1 protein function with a negative predictive value of 95%. 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: May 1, 2024

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