Submissions for variant NM_014625.4(NPHS2):c.954C>T (p.Ala318=)

gnomAD frequency: 0.61660  dbSNP: rs1410592

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000243457	SCV000312206	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000615797	SCV000351498	benign	Nephrotic syndrome, type 2	2018-01-12	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587451	SCV000699388	benign	not provided	2016-07-05	criteria provided, single submitter	clinical testing	Variant summary: The NPHS2 c.954C>T (p.Ala318Ala) variant involves the alteration of a non-conserved nucleotide resulting in a synonymous change. One in silico tool (MutationTaster) predicts a polymorphism outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing, howevere these predictions are yet to be confirmed by the functional studies. This variant was found in 75096/121278 control chromosomes (including 23360 homozygotes) at a frequency of 0.6192055, which is approximately 350 times the estimated maximal expected allele frequency of a pathogenic NPHS2 variant (0.0017678), suggesting this variant is a common benign polymorphism. The variant of interest has also been cited as a polymorphism in published reports (Rachmadi_2015). Taken together, this variant is classified as Benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000587451	SCV001726044	benign	not provided	2025-02-03	criteria provided, single submitter	clinical testing
GeneDx	RCV000587451	SCV001754264	benign	not provided	2019-10-18	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000615797	SCV001754632	benign	Nephrotic syndrome, type 2	2021-07-08	criteria provided, single submitter	clinical testing
Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	RCV000243457	SCV005087342	benign	not specified	2024-07-15	criteria provided, single submitter	clinical testing	This variant is classified as Benign based on local population frequency. This variant was detected in 86% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 80. Only high quality variants are reported.
Breakthrough Genomics, Breakthrough Genomics	RCV000587451	SCV005288592	benign	not provided		criteria provided, single submitter	not provided
Natera, Inc.	RCV001273610	SCV001456810	benign	Steroid-resistant nephrotic syndrome	2020-09-16	no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000243457	SCV001927252	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000243457	SCV001954295	benign	not specified		no assertion criteria provided	clinical testing