chr10-87743589-C-A
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PVS1PM2PP3PP5_Moderate
The NM_001015880.2(PAPSS2):c.1439C>A(p.Ser480Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,854 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 Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001015880.2 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PAPSS2 | NM_001015880.2 | c.1439C>A | p.Ser480Ter | stop_gained | 11/13 | ENST00000456849.2 | |
PAPSS2 | NM_004670.4 | c.1424C>A | p.Ser475Ter | stop_gained | 10/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PAPSS2 | ENST00000456849.2 | c.1439C>A | p.Ser480Ter | stop_gained | 11/13 | 1 | NM_001015880.2 | A1 | |
PAPSS2 | ENST00000361175.8 | c.1424C>A | p.Ser475Ter | stop_gained | 10/12 | 1 | P4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461854Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 727234
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Spondyloepimetaphyseal dysplasia, PAPSS2 type Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 01, 1998 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 13, 2022 | This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser480*) in the PAPSS2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PAPSS2 are known to be pathogenic (PMID: 22791835, 23633440). This premature translational stop signal has been observed in individual(s) with PAPSS2-related conditions (PMID: 9771708, 25594860). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 6686). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at