rs149852592
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_213655.5(WNK1):āc.5739T>Cā(p.Ser1913=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00128 in 1,614,214 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00093 ( 2 hom., cov: 32)
Exomes š: 0.0013 ( 16 hom. )
Consequence
WNK1
NM_213655.5 synonymous
NM_213655.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.925
Genes affected
WNK1 (HGNC:14540): (WNK lysine deficient protein kinase 1) This gene encodes a member of the WNK subfamily of serine/threonine protein kinases. The encoded protein may be a key regulator of blood pressure by controlling the transport of sodium and chloride ions. Mutations in this gene have been associated with pseudohypoaldosteronism type II and hereditary sensory neuropathy type II. Alternatively spliced transcript variants encoding different isoforms have been described but the full-length nature of all of them has yet to be determined.[provided by RefSeq, May 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
?
Variant 12-885787-T-C is Benign according to our data. Variant chr12-885787-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 310832.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-885787-T-C is described in Lovd as [Benign]. Variant chr12-885787-T-C is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=0.925 with no splicing effect.
BS2
?
High Homozygotes in GnomAd4 at 2 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WNK1 | NM_213655.5 | c.5739T>C | p.Ser1913= | synonymous_variant | 19/28 | ENST00000340908.9 | |
WNK1 | NM_018979.4 | c.4983T>C | p.Ser1661= | synonymous_variant | 19/28 | ENST00000315939.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WNK1 | ENST00000340908.9 | c.5739T>C | p.Ser1913= | synonymous_variant | 19/28 | 5 | NM_213655.5 | A2 | |
WNK1 | ENST00000315939.11 | c.4983T>C | p.Ser1661= | synonymous_variant | 19/28 | 1 | NM_018979.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000933 AC: 142AN: 152204Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.00224 AC: 564AN: 251396Hom.: 6 AF XY: 0.00263 AC XY: 358AN XY: 135872
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GnomAD4 exome AF: 0.00132 AC: 1927AN: 1461892Hom.: 16 Cov.: 36 AF XY: 0.00161 AC XY: 1171AN XY: 727248
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GnomAD4 genome ? AF: 0.000932 AC: 142AN: 152322Hom.: 2 Cov.: 32 AF XY: 0.000994 AC XY: 74AN XY: 74484
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2023 | WNK1: BP4, BP7, BS2 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 24, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 07, 2023 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
not specified Benign:1
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
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
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at