rs387907103
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_017813.5(BPNT2):c.559C>T(p.Arg187*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000964 in 1,452,518 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
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )
Consequence
BPNT2
NM_017813.5 stop_gained
NM_017813.5 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 4.16
Genes affected
BPNT2 (HGNC:26019): (3'(2'), 5'-bisphosphate nucleotidase 2) This gene encodes a member of the inositol monophosphatase family. The encoded protein is localized to the Golgi apparatus and catalyzes the hydrolysis of phosphoadenosine phosphate (PAP) to adenosine monophosphate (AMP). Mutations in this gene are a cause of GRAPP type chondrodysplasia with joint dislocations, and a pseudogene of this gene is located on the long arm of chromosome 1. [provided by RefSeq, Dec 2011]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 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 8-56978137-G-A is Pathogenic according to our data. Variant chr8-56978137-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 31092.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BPNT2 | NM_017813.5 | c.559C>T | p.Arg187* | stop_gained | 3/5 | ENST00000262644.9 | NP_060283.3 | |
BPNT2 | XM_047421917.1 | c.559C>T | p.Arg187* | stop_gained | 3/5 | XP_047277873.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BPNT2 | ENST00000262644.9 | c.559C>T | p.Arg187* | stop_gained | 3/5 | 1 | NM_017813.5 | ENSP00000262644.4 | ||
BPNT2 | ENST00000517461.1 | c.201+2022C>T | intron_variant | 5 | ENSP00000430185.1 | |||||
BPNT2 | ENST00000520392.1 | n.85C>T | non_coding_transcript_exon_variant | 2/5 | 2 | ENSP00000428617.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000964 AC: 14AN: 1452518Hom.: 0 Cov.: 28 AF XY: 0.00000415 AC XY: 3AN XY: 723184
GnomAD4 exome
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14
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1452518
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28
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3
AN XY:
723184
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Chondrodysplasia with joint dislocations, gPAPP type Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Oct 23, 2022 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 2012 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Knight Diagnostic Laboratories, Oregon Health and Sciences University | Jul 29, 2019 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Nov 30, 2017 | The R187X variant in the IMPAD1 gene has been reported previously in the homozygous state in two unrelated individuals with IMPAD1-related disorder (Vissers et al., 2011; Nizon et al., 2012). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R187X variant is not observed in large population cohorts (Lek et al., 2016). We interpret R187X as a pathogenic variant. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
Vest4
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at