NM_014625.4(NPHS2):c.59C>T (p.Pro20Leu) AND Nephrotic syndrome, type 2

Germline classification:: Conflicting interpretations of pathogenicity (5 submissions)
Last evaluated:: May 18, 2021
Review status:: criteria provided, conflicting classifications

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000005696.15

Allele description [Variation Report for NM_014625.4(NPHS2):c.59C>T (p.Pro20Leu)]

NM_014625.4(NPHS2):c.59C>T (p.Pro20Leu)

Gene:

NPHS2:NPHS2 stomatin family member, podocin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q25.2

Genomic location:

Preferred name:

NM_014625.4(NPHS2):c.59C>T (p.Pro20Leu)

HGVS:

NC_000001.11:g.179575806G>A
NG_007535.1:g.5144C>T
NM_001297575.2:c.59C>T
NM_014625.4:c.59C>TMANE SELECT
NP_001284504.1:p.Pro20Leu
NP_055440.1:p.Pro20Leu
NP_055440.1:p.Pro20Leu
LRG_887t1:c.59C>T
LRG_887:g.5144C>T
LRG_887p1:p.Pro20Leu
NC_000001.10:g.179544941G>A
NM_014625.2:c.59C>T
NM_014625.3:c.59C>T
Q9NP85:p.Pro20Leu

Protein change:

P20L; PRO20LEU

Links:

UniProtKB: Q9NP85#VAR_010231; OMIM: 604766.0006; dbSNP: rs74315344

NCBI 1000 Genomes Browser:

rs74315344

Molecular consequence:

NM_001297575.2:c.59C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_014625.4:c.59C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Nephrotic syndrome, type 2 (NPHS2)
Synonyms:: Nephrotic syndrome, steroid-resistant, autosomal recessive; Hereditary nephrotic syndrome
Identifiers:: MONDO: MONDO:0010974; MedGen: C1868672; Orphanet: 656; OMIM: 600995

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000025878	OMIM	no assertion criteria provided	Pathogenic (May 1, 2003)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 10742096, 12707396
SCV001254354	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Benign (Apr 27, 2017)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 19406966, 12707396, 22578956, 10742096 Citation Link,
SCV001439909	Institute of Human Genetics, University of Leipzig Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jan 1, 2019)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001737178	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (May 18, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001984407	Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Mar 26, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Clinical features and long-term outcome of nephrotic syndrome associated with heterozygous NPHS1 and NPHS2 mutations.

Caridi G, Gigante M, Ravani P, Trivelli A, Barbano G, Scolari F, Dagnino M, Murer L, Murtas C, Edefonti A, Allegri L, Amore A, Coppo R, Emma F, De Palo T, Penza R, Gesualdo L, Ghiggeri GM.

Clin J Am Soc Nephrol. 2009 Jun;4(6):1065-72. doi: 10.2215/CJN.03910808. Epub 2009 Apr 30.

PubMed [citation]

PMID:: 19406966
PMCID:: PMC2689885

Broadening the spectrum of diseases related to podocin mutations.

Caridi G, Bertelli R, Di Duca M, Dagnino M, Emma F, Onetti Muda A, Scolari F, Miglietti N, Mazzucco G, Murer L, Carrea A, Massella L, Rizzoni G, Perfumo F, Ghiggeri GM.

J Am Soc Nephrol. 2003 May;14(5):1278-86.

PubMed [citation]

PMID:: 12707396

See all PubMed Citations (5)

Details of each submission

From OMIM, SCV000025878.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

In a consanguineous family with autosomal recessive steroid-resistant nephrotic syndrome (600995), Boute et al. (2000) identified a homozygous 59C-T transition in exon 1 of the NPHS2 gene, resulting in a pro20-to-leu (P20L) substitution.

Caridi et al. (2003) identified a heterozygous P20L mutation in 5 unrelated patients with a slightly milder form of NPHS2, 3 of whom showed response to steroid treatment. Although the authors could not exclude another pathogenic mutation, they suggested that heterozygous NPHS2 mutations may be associated with a milder phenotype.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Illumina Laboratory Services, Illumina, SCV001254354.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

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. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Institute of Human Genetics, University of Leipzig Medical Center, SCV001439909.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genome-Nilou Lab, SCV001737178.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital, SCV001984407.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Aug 4, 2024

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