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NM_014625.4(NPHS2):c.413G>A (p.Arg138Gln) AND NPHS2-related disorder

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 31, 2024
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV003944802.3

Allele description [Variation Report for NM_014625.4(NPHS2):c.413G>A (p.Arg138Gln)]

NM_014625.4(NPHS2):c.413G>A (p.Arg138Gln)

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.413G>A (p.Arg138Gln)
HGVS:
  • NC_000001.11:g.179561327C>T
  • NG_007535.1:g.19623G>A
  • NM_001297575.2:c.413G>A
  • NM_014625.4:c.413G>AMANE SELECT
  • NP_001284504.1:p.Arg138Gln
  • NP_055440.1:p.Arg138Gln
  • NP_055440.1:p.Arg138Gln
  • LRG_887t1:c.413G>A
  • LRG_887:g.19623G>A
  • LRG_887p1:p.Arg138Gln
  • NC_000001.10:g.179530462C>T
  • NM_001297575.2:c.413G>A
  • NM_014625.2:c.413G>A
  • NM_014625.3:c.413G>A
  • Q9NP85:p.Arg138Gln
  • p.ARG138GLN
  • p.R138Q
Protein change:
R138Q; ARG138GLN
Links:
UniProtKB: Q9NP85#VAR_010233; OMIM: 604766.0001; dbSNP: rs74315342
NCBI 1000 Genomes Browser:
rs74315342
Molecular consequence:
  • NM_001297575.2:c.413G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_014625.4:c.413G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
NPHS2-related disorder
Synonyms:
NPHS2-related condition
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004769508PreventionGenetics, part of Exact Sciences
no assertion criteria provided
Pathogenic
(Aug 31, 2024) 		germlineclinical testing

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004769508.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The NPHS2 c.413G>A variant is predicted to result in the amino acid substitution p.Arg138Gln. This variant has been reported in the homozygous or compound heterozygous state in many individuals with steroid-resistant nephrotic syndrome and is the most common pathogenic variant in European individuals (commonly referred to as R138Q; Boute et al. 2000. PubMed ID: 10742096; Bouchireb et al. 2013. PubMed ID: 24227627; Malina et al. 2009. PubMed ID: 19495806; Bińczak-Kuleta et al. 2014. PubMed ID: 24856380). Functional studies indicate this variant causes aberrant accumulation in the endoplasmic reticulum instead of localization to the plasma membrane (Roselli et al. 2004. PubMed ID: 14675423). A mouse model hemizygous for this variant developed nephrotic syndrome and showed elevated mRNA expression of the mutant allele and podocin protein loss (Tabatabaeifar et al. 2017. PubMed ID: 29049388). This variant is reported in 0.11% of alleles in individuals of European (non-Finnish) descent in gnomAD. This variant is interpreted as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jan 13, 2025