Submissions for variant NM_002241.5(KCNJ10):c.530A>G (p.Glu177Gly)

gnomAD frequency: 0.00043  dbSNP: rs145947380

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000724333	SCV000227255	uncertain significance	not provided	2014-11-10	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001084650	SCV000349841	uncertain significance	EAST syndrome	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000348162	SCV000349842	uncertain significance	Autosomal recessive nonsyndromic hearing loss 4	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae	RCV001084650	SCV000552193	likely benign	EAST syndrome	2024-01-22	criteria provided, single submitter	clinical testing
GeneDx	RCV000724333	SCV000616991	uncertain significance	not provided	2023-06-26	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000768246	SCV000898773	uncertain significance	Autosomal recessive nonsyndromic hearing loss 4; EAST syndrome	2021-11-01	criteria provided, single submitter	clinical testing	KCNJ10 NM_002241 exon 2 p.Glu177Gly (c.530A>G): This variant has not been reported in the literature but is present in 0.7% (50/6682) of Ashkenazi Jewish alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs145947380). This variant is present in ClinVar (Variation ID: 195165). Evolutionary conservation and computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
CeGaT Center for Human Genetics Tuebingen	RCV000724333	SCV001248565	uncertain significance	not provided	2019-07-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002345601	SCV002644930	benign	Inborn genetic diseases	2024-02-29	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
PreventionGenetics, part of Exact Sciences	RCV004537388	SCV004741133	likely benign	KCNJ10-related disorder	2023-02-17	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).