rs569121553
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_018979.4(WNK1):c.2656C>G(p.Pro886Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000867 in 1,614,096 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 Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P886P) has been classified as Likely benign.
Frequency
Consequence
NM_018979.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WNK1 | NM_018979.4 | c.2656C>G | p.Pro886Ala | missense_variant | 11/28 | ENST00000315939.11 | |
WNK1 | NM_213655.5 | c.3867+1494C>G | intron_variant | ENST00000340908.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WNK1 | ENST00000315939.11 | c.2656C>G | p.Pro886Ala | missense_variant | 11/28 | 1 | NM_018979.4 | P2 | |
WNK1 | ENST00000340908.9 | c.3867+1494C>G | intron_variant | 5 | NM_213655.5 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000658 AC: 10AN: 152086Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251428Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135884
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461892Hom.: 0 Cov.: 35 AF XY: 0.00000550 AC XY: 4AN XY: 727248
GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152204Hom.: 0 Cov.: 31 AF XY: 0.0000672 AC XY: 5AN XY: 74408
ClinVar
Submissions by phenotype
Pseudohypoaldosteronism type 2C;C2752089:Neuropathy, hereditary sensory and autonomic, type 2A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 17, 2018 | This sequence change replaces proline with alanine at codon 886 of the WNK1 protein (p.Pro886Ala). The proline residue is highly conserved and there is a small physicochemical difference between proline and alanine. This variant is present in population databases (rs569121553, 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: "Probably Damaging"; Align-GVGD: "Class C0"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at