NM_014625.4(NPHS2):c.29G>C (p.Arg10Thr) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 21, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003226802.1

Allele description [Variation Report for NM_014625.4(NPHS2):c.29G>C (p.Arg10Thr)]

NM_014625.4(NPHS2):c.29G>C (p.Arg10Thr)

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.29G>C (p.Arg10Thr)

HGVS:

NC_000001.11:g.179575836C>G
NG_007535.1:g.5114G>C
NM_001297575.2:c.29G>C
NM_014625.4:c.29G>CMANE SELECT
NP_001284504.1:p.Arg10Thr
NP_055440.1:p.Arg10Thr
NP_055440.1:p.Arg10Thr
LRG_887t1:c.29G>C
LRG_887:g.5114G>C
LRG_887p1:p.Arg10Thr
NC_000001.10:g.179544971C>G
NM_014625.3:c.29G>C

Protein change:

R10T

Molecular consequence:

NM_001297575.2:c.29G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_014625.4:c.29G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003923060	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Mar 21, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 18823551, 24500309 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003923060

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Mar 21, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

NPHS2 variation in focal and segmental glomerulosclerosis.

Tonna SJ, Needham A, Polu K, Uscinski A, Appel GB, Falk RJ, Katz A, Al-Waheeb S, Kaplan BS, Jerums G, Savige J, Harmon J, Zhang K, Curhan GC, Pollak MR.

BMC Nephrol. 2008 Sep 29;9:13. doi: 10.1186/1471-2369-9-13.

PubMed [citation]

PMID:: 18823551
PMCID:: PMC2569023

Podocyte-associated gene mutation screening in a heterogeneous cohort of patients with sporadic focal segmental glomerulosclerosis.

Laurin LP, Lu M, Mottl AK, Blyth ER, Poulton CJ, Weck KE.

Nephrol Dial Transplant. 2014 Nov;29(11):2062-9. doi: 10.1093/ndt/gft532. Epub 2014 Feb 4.

PubMed [citation]

PMID:: 24500309

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV003923060.1

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

Description

Variant summary: NPHS2 c.29G>C (p.Arg10Thr) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 69986 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.29G>C has been reported in the literature as a variant of uncertain significance in individuals affected with sporadic Nephrotic Syndrome, Type 2 with focal segmental glomerulosclerosis who carry a second variant of conflicting pathogenicity (p.R229Q) or carry no second NPHS2 variant (Tonna_2008, Laurin_2014). These reports do not provide unequivocal conclusions about association of the variant with Nephrotic Syndrome, Type 2. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.

#	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

Last Updated: May 13, 2023

ClinVar

Relating variation to medicine