rs606231243
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_001015880.2(PAPSS2):c.477_480dup(p.Lys161ArgfsTer6) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. D159D) has been classified as Benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
PAPSS2
NM_001015880.2 frameshift
NM_001015880.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.95
Genes affected
PAPSS2 (HGNC:8604): (3'-phosphoadenosine 5'-phosphosulfate synthase 2) Sulfation is a common modification of endogenous (lipids, proteins, and carbohydrates) and exogenous (xenobiotics and drugs) compounds. In mammals, the sulfate source is 3'-phosphoadenosine 5'-phosphosulfate (PAPS), created from ATP and inorganic sulfate. Two different tissue isoforms encoded by different genes synthesize PAPS. This gene encodes one of the two PAPS synthetases. Defects in this gene cause the Pakistani type of spondyloepimetaphyseal dysplasia. Two alternatively spliced transcript variants that encode different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 10-87714137-G-GACGT is Pathogenic according to our data. Variant chr10-87714137-G-GACGT is described in ClinVar as [Pathogenic]. Clinvar id is 39645.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PAPSS2 | NM_001015880.2 | c.477_480dup | p.Lys161ArgfsTer6 | frameshift_variant | 4/13 | ENST00000456849.2 | |
PAPSS2 | NM_004670.4 | c.477_480dup | p.Lys161ArgfsTer6 | frameshift_variant | 4/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PAPSS2 | ENST00000456849.2 | c.477_480dup | p.Lys161ArgfsTer6 | frameshift_variant | 4/13 | 1 | NM_001015880.2 | A1 | |
PAPSS2 | ENST00000361175.8 | c.477_480dup | p.Lys161ArgfsTer6 | frameshift_variant | 4/12 | 1 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Spondyloepimetaphyseal dysplasia, PAPSS2 type Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 01, 2012 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at