rs74315346

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PM2PM5PP2PP3_StrongPP5

The NM_014625.4(NPHS2):c.479A>T(p.Asp160Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D160G) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NPHS2
NM_014625.4 missense

Scores

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 6.00

Publications

8 publications found

Variant links:

Genes affected

NPHS2 (HGNC:13394): (NPHS2 stomatin family member, podocin) This gene encodes a protein that plays a role in the regulation of glomerular permeability. Mutations in this gene cause steroid-resistant nephrotic syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

NPHS2 Gene-Disease associations (from GenCC):

nephrotic syndrome, type 2
Inheritance: AR, AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Myriad Women’s Health, Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina, G2P
familial idiopathic steroid-resistant nephrotic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

NPHS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 10 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr1-179559734-T-C is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 5367.Status of the report is criteria_provided_single_submitter, 1 stars.

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 29 curated pathogenic missense variants (we use a threshold of 10). The gene has 4 curated benign missense variants. Gene score misZ: 0.68612 (below the threshold of 3.09). Trascript score misZ: 0.038296 (below the threshold of 3.09). GenCC associations: The gene is linked to nephrotic syndrome, type 2, familial idiopathic steroid-resistant nephrotic syndrome.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.962

PP5

Variant 1-179559734-T-A is Pathogenic according to our data. Variant chr1-179559734-T-A is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 599118.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPHS2	NM_014625.4 link	c.479A>T	p.Asp160Val	missense_variant	Exon 4 of 8	ENST00000367615.9	NP_055440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPHS2	ENST00000367615.9 link	c.479A>T	p.Asp160Val	missense_variant	Exon 4 of 8	1	NM_014625.4	ENSP00000356587.4
NPHS2	ENST00000367616.4 link	c.479A>T	p.Asp160Val	missense_variant	Exon 4 of 7	1		ENSP00000356588.4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1438506

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

713266

African (AFR)

AF:

0.00

AC:

AN:

32872

American (AMR)

AF:

0.00

AC:

AN:

42934

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25592

East Asian (EAS)

AF:

0.00

AC:

AN:

38992

South Asian (SAS)

AF:

0.00

AC:

AN:

83004

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52040

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1097940

Other (OTH)

AF:

0.00

AC:

AN:

59402

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Nephrotic syndrome, type 2

Pathogenic:1

May 17, 2018

Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare

Significance:Likely pathogenic

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Pathogenic

0.50

BayesDel_noAF

Pathogenic

0.49

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.96

D;.

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Pathogenic

0.54

MetaRNN

Pathogenic

0.96

D;D

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

3.6

H;H

PhyloP100

6.0

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-8.2

D;D

REVEL

Pathogenic

0.96

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.97

MutPred

0.73

Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);

MVP

0.96

MPC

1.1

ClinPred

1.0

GERP RS

5.4

Varity_R

0.96

gMVP

0.97

Mutation Taster

=12/88

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over