4-105370590-GAA-GAAA
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_176869.3(PPA2):c.976+246dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000694 in 965,468 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0000068 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000081 ( 0 hom. )
Consequence
PPA2
NM_176869.3 intron
NM_176869.3 intron
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.0850
Publications
0 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), Laboratory for Molecular Medicine, Ambry Genetics
- dilated cardiomyopathyInheritance: AR Classification: STRONG Submitted by: ClinGen
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_176869.3. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PPA2 | NM_176869.3 | MANE Select | c.976+246dupT | intron | N/A | NP_789845.1 | Q9H2U2-1 | ||
| PPA2 | NM_006903.4 | c.889+246dupT | intron | N/A | NP_008834.3 | Q9H2U2-3 | |||
| PPA2 | NM_176866.2 | c.670+246dupT | intron | N/A | NP_789842.2 | Q9H2U2-6 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PPA2 | ENST00000341695.10 | TSL:1 MANE Select | c.976+246_976+247insT | intron | N/A | ENSP00000343885.5 | Q9H2U2-1 | ||
| PPA2 | ENST00000348706.9 | TSL:1 | c.889+246_889+247insT | intron | N/A | ENSP00000313061.8 | Q9H2U2-3 | ||
| PPA2 | ENST00000432483.6 | TSL:1 | c.670+246_670+247insT | intron | N/A | ENSP00000389957.2 | Q9H2U2-6 |
Frequencies
GnomAD3 genomes 0.00000680 AC: 1AN: 146978Hom.: 0 Cov.: 30 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
146978
Hom.:
Cov.:
30
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.0000806 AC: 66AN: 818490Hom.: 0 Cov.: 0 AF XY: 0.0000687 AC XY: 26AN XY: 378412 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
66
AN:
818490
Hom.:
Cov.:
0
AF XY:
AC XY:
26
AN XY:
378412
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
3
AN:
15476
American (AMR)
AF:
AC:
0
AN:
966
Ashkenazi Jewish (ASJ)
AF:
AC:
2
AN:
5088
East Asian (EAS)
AF:
AC:
1
AN:
3526
South Asian (SAS)
AF:
AC:
2
AN:
16184
European-Finnish (FIN)
AF:
AC:
0
AN:
274
Middle Eastern (MID)
AF:
AC:
0
AN:
1600
European-Non Finnish (NFE)
AF:
AC:
58
AN:
748564
Other (OTH)
AF:
AC:
0
AN:
26812
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.282
Heterozygous variant carriers
0
9
18
26
35
44
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome 0.00000680 AC: 1AN: 146978Hom.: 0 Cov.: 30 AF XY: 0.0000140 AC XY: 1AN XY: 71284 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
1
AN:
146978
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
71284
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
39946
American (AMR)
AF:
AC:
1
AN:
14810
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3452
East Asian (EAS)
AF:
AC:
0
AN:
5124
South Asian (SAS)
AF:
AC:
0
AN:
4700
European-Finnish (FIN)
AF:
AC:
0
AN:
8996
Middle Eastern (MID)
AF:
AC:
0
AN:
304
European-Non Finnish (NFE)
AF:
AC:
0
AN:
66734
Other (OTH)
AF:
AC:
0
AN:
2018
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.325
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
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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