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NM_018979.4(WNK1):c.217A>G (p.Thr73Ala) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
May 22, 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:
RCV000533336.6

Allele description [Variation Report for NM_018979.4(WNK1):c.217A>G (p.Thr73Ala)]

NM_018979.4(WNK1):c.217A>G (p.Thr73Ala)

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.217A>G (p.Thr73Ala)
HGVS:
  • NC_000012.12:g.753782A>G
  • NG_007984.3:g.5724A>G
  • NM_001184985.2:c.217A>G
  • NM_014823.3:c.217A>G
  • NM_018979.4:c.217A>GMANE SELECT
  • NM_213655.5:c.217A>G
  • NP_001171914.1:p.Thr73Ala
  • NP_055638.2:p.Thr73Ala
  • NP_061852.3:p.Thr73Ala
  • NP_998820.3:p.Thr73Ala
  • LRG_247t1:c.217A>G
  • LRG_247t2:c.217A>G
  • LRG_247:g.5724A>G
  • LRG_247p1:p.Thr73Ala
  • LRG_247p2:p.Thr73Ala
  • NC_000012.11:g.862948A>G
  • NM_018979.3:c.217A>G
Protein change:
T73A
Links:
dbSNP: rs1038270127
NCBI 1000 Genomes Browser:
rs1038270127
Molecular consequence:
  • NM_001184985.2:c.217A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_014823.3:c.217A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_018979.4:c.217A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_213655.5:c.217A>G - 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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000649405Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(May 22, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000649405.4

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

Description

This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 73 of the WNK1 protein (p.Thr73Ala). 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 WNK1 protein function. ClinVar contains an entry for this variant (Variation ID: 471173). This variant has not been reported in the literature in individuals affected with WNK1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%).

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

Last Updated: Mar 5, 2024