NM_014625.4(NPHS2):c.965G>C (p.Arg322Pro) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Mar 29, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001788442.4

Allele description [Variation Report for NM_014625.4(NPHS2):c.965G>C (p.Arg322Pro)]

NM_014625.4(NPHS2):c.965G>C (p.Arg322Pro)

Genes:

NPHS2:NPHS2 stomatin family member, podocin [Gene - OMIM - HGNC]
AXDND1:axonemal dynein light chain domain containing 1 [Gene - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q25.2

Genomic location:

Preferred name:

NM_014625.4(NPHS2):c.965G>C (p.Arg322Pro)

HGVS:

NC_000001.11:g.179551360C>G
NG_007535.1:g.29590G>C
NG_033075.1:g.190641C>G
NM_001297575.2:c.761G>C
NM_014625.4:c.965G>CMANE SELECT
NM_144696.6:c.3032-3152C>GMANE SELECT
NP_001284504.1:p.Arg254Pro
NP_055440.1:p.Arg322Pro
NP_055440.1:p.Arg322Pro
LRG_887t1:c.965G>C
LRG_887:g.29590G>C
LRG_887p1:p.Arg322Pro
NC_000001.10:g.179520495C>G
NM_014625.3:c.965G>C

Protein change:

R254P

Links:

dbSNP: rs776859868

NCBI 1000 Genomes Browser:

rs776859868

Molecular consequence:

NM_144696.6:c.3032-3152C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001297575.2:c.761G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_014625.4:c.965G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002030924	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Nov 22, 2021)	germline	clinical testing	Citation Link,
SCV004229813	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Uncertain significance (Mar 29, 2023)	unknown	clinical testing	PubMed (6) [See all records that cite these PMIDs] 30260545, 27193387, 19268410, 30280213, 25349199, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002030924

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Nov 22, 2021)

germline

clinical testing

Citation Link,

SCV004229813

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Uncertain significance
(Mar 29, 2023)

unknown

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

The mutation-dependent pathogenicity of NPHS2 p.R229Q: A guide for clinical assessment.

Mikó Á, K Menyhárd D, Kaposi A, Antignac C, Tory K.

Hum Mutat. 2018 Dec;39(12):1854-1860. doi: 10.1002/humu.23660. Epub 2018 Oct 22. Review.

PubMed [citation]

PMID:: 30260545

In silico Structural characterization of podocin and assessment of nephrotic syndrome-associated podocin mutants.

Mulukala SK, Nishad R, Kolligundla LP, Saleem MA, Prabhu NP, Pasupulati AK.

IUBMB Life. 2016 Jul;68(7):578-88. doi: 10.1002/iub.1515. Epub 2016 May 18.

PubMed [citation]

PMID:: 27193387

See all PubMed Citations (6)

Details of each submission

From GeneDx, SCV002030924.2

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

Description

Observed with the R229Q variant in patients with steroid-resistant nephrotic syndrome in published literature (Sharma S et al., 2008; Choudhry S et al., 2009); Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 19484379, 30260545, 27193387, 19268410)

#	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

From Athena Diagnostics, SCV004229813.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is uninformative in assessment of its pathogenicity (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual with clinical features associated with this gene. Computational tools predict that this variant is damaging.

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

Last Updated: Sep 1, 2024

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