ClinVar Miner

Submissions for variant NM_018979.4(WNK1):c.5968C>T (p.Pro1990Ser)

gnomAD frequency: 0.00009  dbSNP: rs577801497
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000260785 SCV000375090 benign Pseudohypoaldosteronism type 2C 2018-01-13 criteria provided, single submitter clinical testing 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001506204 SCV001711123 likely benign Neuropathy, hereditary sensory and autonomic, type 2A; Pseudohypoaldosteronism type 2C 2024-01-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV002365356 SCV002665052 likely benign Inborn genetic diseases 2021-10-29 criteria provided, single submitter clinical testing 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004782351 SCV005394841 likely benign not specified 2024-09-23 criteria provided, single submitter clinical testing Variant summary: WNK1 c.5968C>T (p.Pro1990Ser) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00023 in 251306 control chromosomes, predominantly at a frequency of 0.0032 within the East Asian subpopulation in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database exceeds the estimated maximal expected allele frequency for a pathogenic variant in WNK1 causing Neuropathy, Hereditary Sensory And Autonomic, Type 2A phenotype. To our knowledge, no occurrence of c.5968C>T in individuals affected with Neuropathy, Hereditary Sensory And Autonomic, Type 2A and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 306614). Based on the evidence outlined above, the variant was classified as likely benign.

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