rs72650768
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4_StrongBP6
The NM_213655.5(WNK1):c.7380C>A(p.Ser2460Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000195 in 1,614,174 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 nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Synonymous variant affecting the same amino acid position (i.e. S2460S) has been classified as Likely benign.
Frequency
Consequence
NM_213655.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WNK1 | NM_213655.5 | c.7380C>A | p.Ser2460Arg | missense_variant | 26/28 | ENST00000340908.9 | |
WNK1 | NM_018979.4 | c.6624C>A | p.Ser2208Arg | missense_variant | 26/28 | ENST00000315939.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WNK1 | ENST00000340908.9 | c.7380C>A | p.Ser2460Arg | missense_variant | 26/28 | 5 | NM_213655.5 | A2 | |
WNK1 | ENST00000315939.11 | c.6624C>A | p.Ser2208Arg | missense_variant | 26/28 | 1 | NM_018979.4 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00112 AC: 170AN: 152180Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000306 AC: 77AN: 251416Hom.: 0 AF XY: 0.000191 AC XY: 26AN XY: 135880
GnomAD4 exome AF: 0.0000992 AC: 145AN: 1461876Hom.: 0 Cov.: 31 AF XY: 0.0000798 AC XY: 58AN XY: 727244
GnomAD4 genome AF: 0.00112 AC: 170AN: 152298Hom.: 0 Cov.: 32 AF XY: 0.000953 AC XY: 71AN XY: 74478
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 30, 2022 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 02, 2015 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 20, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Pseudohypoaldosteronism type 2C;C2752089:Neuropathy, hereditary sensory and autonomic, type 2A Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at