rs1553316670
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_014625.4(NPHS2):c.28dupA(p.Arg10LysfsTer60) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 34)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
NPHS2
NM_014625.4 frameshift
NM_014625.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.399
Publications
0 publications found
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 2Inheritance: AR, AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Ambry Genetics, G2P
- familial idiopathic steroid-resistant nephrotic syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 12 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 131 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-179575836-C-CT is Pathogenic according to our data. Variant chr1-179575836-C-CT is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 447878.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_014625.4. You can select a different transcript below to see updated ACMG assignments.
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| NPHS2 | TSL:1 MANE Select | c.28dupA | p.Arg10LysfsTer60 | frameshift | Exon 1 of 8 | ENSP00000356587.4 | Q9NP85-1 | ||
| NPHS2 | TSL:1 | c.28dupA | p.Arg10LysfsTer60 | frameshift | Exon 1 of 7 | ENSP00000356588.4 | Q9NP85-2 | ||
| NPHS2 | c.28dupA | p.Arg10LysfsTer60 | frameshift | Exon 1 of 6 | ENSP00000572315.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
34
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1289862Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0AN XY: 633044
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1289862
Hom.:
Cov.:
36
AF XY:
AC XY:
0
AN XY:
633044
African (AFR)
AF:
AC:
0
AN:
25732
American (AMR)
AF:
AC:
0
AN:
18702
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
18452
East Asian (EAS)
AF:
AC:
0
AN:
32176
South Asian (SAS)
AF:
AC:
0
AN:
60662
European-Finnish (FIN)
AF:
AC:
0
AN:
36848
Middle Eastern (MID)
AF:
AC:
0
AN:
5002
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1039260
Other (OTH)
AF:
AC:
0
AN:
53028
GnomAD4 genome
GnomAD4 genome
Cov.:
34
ClinVar
ClinVar submissions
View on ClinVar Significance:Likely pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
not provided (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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