Submissions for variant NM_018979.4(WNK1):c.7021G>A (p.Gly2341Ser)

gnomAD frequency: 0.00062  dbSNP: rs146042595

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000291824	SCV000375159	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.
Invitae	RCV000542452	SCV000649469	likely benign	Neuropathy, hereditary sensory and autonomic, type 2A; Pseudohypoaldosteronism type 2C	2024-01-24	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001546004	SCV001160155	uncertain significance	not provided	2023-08-28	criteria provided, single submitter	clinical testing	The WNK1 c.7801G>A; p.Gly2601Ser variant (rs146042595), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 306664). This variant is found in the general population with an overall allele frequency of 0.044% (125/282,838 alleles, including a single homozygote) in the Genome Aggregation Database. The glycine at codon 2601 is weakly conserved, and computational analyses predict that this variant is neutral (REVEL: 0.053). Due to limited information, the clinical significance of the p.Gly2601Ser variant is uncertain at this time.
GeneDx	RCV001546004	SCV001765439	likely benign	not provided	2020-07-08	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Mayo Clinic Laboratories, Mayo Clinic	RCV001546004	SCV002541182	uncertain significance	not provided	2022-03-10	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002411199	SCV002668974	uncertain significance	Inborn genetic diseases	2021-09-20	criteria provided, single submitter	clinical testing	The p.G2593S variant (also known as c.7777G>A), located in coding exon 28 of the WNK1 gene, results from a G to A substitution at nucleotide position 7777. The glycine at codon 2593 is replaced by serine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and serine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.