rs201766777
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PP2PP3BP4BP6
The NM_018979.4(WNK1):c.5869C>T(p.Arg1957Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000314 in 1,614,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1957H) has been classified as Likely benign.
Frequency
Consequence
NM_018979.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
WNK1 | NM_213655.5 | c.6625C>T | p.Arg2209Cys | missense_variant | 24/28 | ENST00000340908.9 | NP_998820.3 | |
WNK1 | NM_018979.4 | c.5869C>T | p.Arg1957Cys | missense_variant | 24/28 | ENST00000315939.11 | NP_061852.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
WNK1 | ENST00000340908.9 | c.6625C>T | p.Arg2209Cys | missense_variant | 24/28 | 5 | NM_213655.5 | ENSP00000341292.5 | ||
WNK1 | ENST00000315939.11 | c.5869C>T | p.Arg1957Cys | missense_variant | 24/28 | 1 | NM_018979.4 | ENSP00000313059.6 |
Frequencies
GnomAD3 genomes AF: 0.000243 AC: 37AN: 152108Hom.: 0 Cov.: 29
GnomAD3 exomes AF: 0.000394 AC: 99AN: 251330Hom.: 1 AF XY: 0.000390 AC XY: 53AN XY: 135826
GnomAD4 exome AF: 0.000322 AC: 470AN: 1461864Hom.: 0 Cov.: 31 AF XY: 0.000319 AC XY: 232AN XY: 727232
GnomAD4 genome AF: 0.000243 AC: 37AN: 152226Hom.: 0 Cov.: 29 AF XY: 0.000134 AC XY: 10AN XY: 74416
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 26, 2022 | The p.R2209C variant (also known as c.6625C>T), located in coding exon 24 of the WNK1 gene, results from a C to T substitution at nucleotide position 6625. The arginine at codon 2209 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Pseudohypoaldosteronism type 2C Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Pseudohypoaldosteronism type 2C;C2752089:Neuropathy, hereditary sensory and autonomic, type 2A Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 16, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at