NM_018979.4(WNK1):c.4703A>C (p.His1568Pro) AND multiple conditions

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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 30, 2019
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:: RCV000697909.7

Allele description

NM_018979.4(WNK1):c.4703A>C (p.His1568Pro)

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_018979.4(WNK1):c.4703A>C (p.His1568Pro)

HGVS:

NC_000012.12:g.885507A>C
NG_007984.3:g.137449A>C
NM_001184985.2:c.5483A>C
NM_014823.3:c.3962A>C
NM_018979.4:c.4703A>CMANE SELECT
NM_213655.5:c.5459A>C
NP_001171914.1:p.His1828Pro
NP_055638.2:p.His1321Pro
NP_061852.3:p.His1568Pro
NP_998820.3:p.His1820Pro
NP_998820.3:p.His1820Pro
LRG_247t1:c.4703A>C
LRG_247t2:c.5459A>C
LRG_247:g.137449A>C
LRG_247p1:p.His1568Pro
LRG_247p2:p.His1820Pro
NC_000012.11:g.994673A>C
NM_018979.3:c.4703A>C
NM_213655.4:c.5459A>C

Protein change:

H1321P

Links:

dbSNP: rs776834411

NCBI 1000 Genomes Browser:

rs776834411

Molecular consequence:

NM_001184985.2:c.5483A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_014823.3:c.3962A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_018979.4:c.4703A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_213655.5:c.5459A>C - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000826543	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 30, 2019)	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

SCV000826543

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 30, 2019)

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, SCV000826543.6

#	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 histidine with proline at codon 1568 of the WNK1 protein (p.His1568Pro). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and proline. This variant is present in population databases (rs776834411, ExAC 0.01%). This variant has not been reported in the literature in individuals with WNK1-related disease. 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). 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: Mar 16, 2024

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