ClinVar Miner

Submissions for variant NM_002241.5(KCNJ10):c.136G>A (p.Asp46Asn)

gnomAD frequency: 0.00146  dbSNP: rs141553756
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001085543 SCV000287321 likely benign EAST syndrome 2024-01-29 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000712154 SCV000341131 uncertain significance not provided 2016-05-18 criteria provided, single submitter clinical testing
GeneDx RCV000374787 SCV000490578 uncertain significance not specified 2016-06-30 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the KCNJ10 gene. The D46N variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The D46N variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project but the 1000 Genomes Project reports it was observed in 2/1322 (0.2%) alleles from individuals of African background. The D46N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved in mammals. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Athena Diagnostics RCV000712154 SCV000842579 uncertain significance not provided 2018-08-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV002317765 SCV000849884 uncertain significance Inborn genetic diseases 2018-06-12 criteria provided, single submitter clinical testing The p.D46N variant (also known as c.136G>A), located in coding exon 1 of the KCNJ10 gene, results from a G to A substitution at nucleotide position 136. The aspartic acid at codon 46 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is not well conserved in available 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.
Illumina Laboratory Services, Illumina RCV001097719 SCV001254024 uncertain significance Autosomal recessive nonsyndromic hearing loss 4 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina RCV001085543 SCV001254025 uncertain significance EAST syndrome 2017-05-13 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
PreventionGenetics, part of Exact Sciences RCV004541386 SCV004779382 likely benign KCNJ10-related disorder 2020-09-14 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
New York Genome Center RCV001255129 SCV001431223 uncertain significance Seizure; Intellectual disability 2019-12-24 no assertion criteria provided clinical testing

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