rs147099510
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP2BP4_StrongBP6_Very_StrongBS2
The NM_213655.5(WNK1):āc.3700A>Gā(p.Ile1234Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00143 in 1,614,186 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Consequence
NM_213655.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -15 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WNK1 | NM_213655.5 | c.3700A>G | p.Ile1234Val | missense_variant | 11/28 | ENST00000340908.9 | |
WNK1 | NM_018979.4 | c.2206A>G | p.Ile736Val | missense_variant | 9/28 | ENST00000315939.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WNK1 | ENST00000340908.9 | c.3700A>G | p.Ile1234Val | missense_variant | 11/28 | 5 | NM_213655.5 | A2 | |
WNK1 | ENST00000315939.11 | c.2206A>G | p.Ile736Val | missense_variant | 9/28 | 1 | NM_018979.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00118 AC: 179AN: 152200Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00185 AC: 464AN: 251464Hom.: 6 AF XY: 0.00227 AC XY: 308AN XY: 135904
GnomAD4 exome AF: 0.00146 AC: 2130AN: 1461868Hom.: 16 Cov.: 31 AF XY: 0.00164 AC XY: 1192AN XY: 727234
GnomAD4 genome ? AF: 0.00118 AC: 179AN: 152318Hom.: 0 Cov.: 32 AF XY: 0.00117 AC XY: 87AN XY: 74490
ClinVar
Submissions by phenotype
not provided Benign:3
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | WNK1: BP4, BS2 - |
Pseudohypoaldosteronism type 2C Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 19, 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
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 27, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at