NM_022089.4:c.1101_1102dupGA
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_022089.4(ATP13A2):c.1101_1102dupGA(p.Thr368ArgfsTer29) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,492 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. T368T) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
ATP13A2
NM_022089.4 frameshift
NM_022089.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.251
Publications
5 publications found
Genes affected
ATP13A2 (HGNC:30213): (ATPase cation transporting 13A2) This gene encodes a member of the P5 subfamily of ATPases which transports inorganic cations as well as other substrates. Mutations in this gene are associated with Kufor-Rakeb syndrome (KRS), also referred to as Parkinson disease 9. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Nov 2008]
ATP13A2 Gene-Disease associations (from GenCC):
- Kufor-Rakeb syndromeInheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Illumina, Genomics England PanelApp, G2P, ClinGen
- autosomal recessive spastic paraplegia type 78Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)
- parkinsonism due to ATP13A2 deficiencyInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 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 1-16997112-G-GTC is Pathogenic according to our data. Variant chr1-16997112-G-GTC is described in ClinVar as Pathogenic. ClinVar VariationId is 30833.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_022089.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ATP13A2 | NM_022089.4 | MANE Select | c.1101_1102dupGA | p.Thr368ArgfsTer29 | frameshift | Exon 12 of 29 | NP_071372.1 | ||
| ATP13A2 | NM_001141973.3 | c.1086_1087dupGA | p.Thr363ArgfsTer29 | frameshift | Exon 12 of 29 | NP_001135445.1 | |||
| ATP13A2 | NM_001141974.3 | c.1086_1087dupGA | p.Thr363ArgfsTer29 | frameshift | Exon 12 of 27 | NP_001135446.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ATP13A2 | ENST00000326735.13 | TSL:1 MANE Select | c.1101_1102dupGA | p.Thr368ArgfsTer29 | frameshift | Exon 12 of 29 | ENSP00000327214.8 | ||
| ATP13A2 | ENST00000452699.5 | TSL:1 | c.1086_1087dupGA | p.Thr363ArgfsTer29 | frameshift | Exon 12 of 29 | ENSP00000413307.1 | ||
| ATP13A2 | ENST00000341676.9 | TSL:1 | c.1086_1087dupGA | p.Thr363ArgfsTer29 | frameshift | Exon 12 of 27 | ENSP00000341115.5 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
31
GnomAD2 exomes AF: 0.00000398 AC: 1AN: 250970 AF XY: 0.00000736 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
250970
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
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Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461492Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727070 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461492
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
727070
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33478
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
1
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
53076
Middle Eastern (MID)
AF:
AC:
0
AN:
5730
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1112006
Other (OTH)
AF:
AC:
0
AN:
60384
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
31
ClinVar
ClinVar submissions as Germline
Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Kufor-Rakeb syndrome (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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