Submissions for variant NM_024426.6(WT1):c.609C>T (p.Asn203=)

gnomAD frequency: 0.13287  dbSNP: rs2234583

Total submissions: 17

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000247609	SCV000341870	benign	not specified	2016-05-24	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000393785	SCV000371460	benign	Nephrotic syndrome, type 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 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.
Illumina Laboratory Services, Illumina	RCV000348640	SCV000371462	benign	Wilms tumor 1	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.
Illumina Laboratory Services, Illumina	RCV000403336	SCV000371463	benign	Meacham 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 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.
GeneDx	RCV000247609	SCV000518970	benign	not specified	2016-04-26	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Athena Diagnostics	RCV000576729	SCV000677586	benign	Drash syndrome; Frasier syndrome; Nephrotic syndrome, type 4; Wilms tumor 1	2017-04-14	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586923	SCV000699505	benign	not provided	2016-05-26	criteria provided, single submitter	clinical testing	Variant summary: The WT1 c.594C>T (p.Asn198Asn) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a polymorphism outcome for this variant along with 4/5 in silico splice prediction tools predicting the variant not to have an impact on splicing. This variant was found in 9132/113272 control chromosomes (598 homozygotes), predominantly observed in the African subpopulation (366 homozygotes) at a frequency of 0.2917204 (2713/9300). This frequency greatly exceeds the estimated maximal expected allele frequency of a pathogenic WT1 variant (0.0000094), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. Taken together, this variant is classified as Benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001517367	SCV001725847	benign	Drash syndrome; Frasier syndrome; Wilms tumor 1; 11p partial monosomy syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002244668	SCV002515069	benign	Drash syndrome	2021-12-05	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002244667	SCV002515070	benign	Frasier syndrome	2021-12-05	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000403336	SCV002515071	benign	Meacham syndrome	2021-12-05	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000393785	SCV002515072	benign	Nephrotic syndrome, type 4	2021-12-05	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000348640	SCV002515073	benign	Wilms tumor 1	2021-12-05	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000348640	SCV004016263	benign	Wilms tumor 1	2023-07-07	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV003588605	SCV004360960	benign	Nephroblastoma	2019-03-28	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000586923	SCV005316016	benign	not provided		criteria provided, single submitter	not provided
PreventionGenetics, part of Exact Sciences	RCV004547639	SCV000314316	benign	WT1-related disorder	2022-06-02	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).