rs1057516414
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_014625.4(NPHS2):c.685C>T(p.Arg229Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000684 in 1,461,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. R229R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_014625.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NPHS2 | NM_014625.4 | c.685C>T | p.Arg229Ter | stop_gained | 5/8 | ENST00000367615.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPHS2 | ENST00000367615.9 | c.685C>T | p.Arg229Ter | stop_gained | 5/8 | 1 | NM_014625.4 | P1 | |
NPHS2 | ENST00000367616.4 | c.535-2549C>T | intron_variant | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461708Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727134
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Nephrotic syndrome, type 2 Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Jun 18, 2023 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Jan 18, 2016 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | This sequence change creates a premature translational stop signal (p.Arg229*) in the NPHS2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NPHS2 are known to be pathogenic (PMID: 10742096, 14701729, 15253708, 23595123). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with steroid resistant nephrotic syndrome (PMID: 24227627). ClinVar contains an entry for this variant (Variation ID: 370340). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at