4-105396272-C-T
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_176869.3(PPA2):c.846G>A(p.Lys282Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
PPA2
NM_176869.3 synonymous
NM_176869.3 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.173
Publications
36 publications found
Genes affected
PPA2 (HGNC:28883): (inorganic pyrophosphatase 2) The protein encoded by this gene is localized to the mitochondrion, is highly similar to members of the inorganic pyrophosphatase (PPase) family, and contains the signature sequence essential for the catalytic activity of PPase. PPases catalyze the hydrolysis of pyrophosphate to inorganic phosphate, which is important for the phosphate metabolism of cells. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]
PPA2 Gene-Disease associations (from GenCC):
- sudden cardiac failure, infantileInheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP7
Synonymous conserved (PhyloP=-0.173 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| PPA2 | NM_176869.3 | c.846G>A | p.Lys282Lys | synonymous_variant | Exon 9 of 12 | ENST00000341695.10 | NP_789845.1 | |
| PPA2 | NM_006903.4 | c.759G>A | p.Lys253Lys | synonymous_variant | Exon 8 of 11 | NP_008834.3 | ||
| PPA2 | NM_176866.2 | c.540G>A | p.Lys180Lys | synonymous_variant | Exon 5 of 8 | NP_789842.2 | ||
| PPA2 | NM_176867.3 | c.348G>A | p.Lys116Lys | synonymous_variant | Exon 3 of 6 | NP_789843.2 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| PPA2 | ENST00000341695.10 | c.846G>A | p.Lys282Lys | synonymous_variant | Exon 9 of 12 | 1 | NM_176869.3 | ENSP00000343885.5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1439990Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 716394
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1439990
Hom.:
Cov.:
30
AF XY:
AC XY:
0
AN XY:
716394
African (AFR)
AF:
AC:
0
AN:
33126
American (AMR)
AF:
AC:
0
AN:
41876
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25698
East Asian (EAS)
AF:
AC:
0
AN:
38642
South Asian (SAS)
AF:
AC:
0
AN:
82164
European-Finnish (FIN)
AF:
AC:
0
AN:
52970
Middle Eastern (MID)
AF:
AC:
0
AN:
5434
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1100604
Other (OTH)
AF:
AC:
0
AN:
59476
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
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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