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GeneBe

rs730880302

chr1-20650512-A-AAGTT

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5

The NM_032409.3(PINK1):c.1570_1573dup(p.Asp525ValfsTer38) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Consequence

PINK1
NM_032409.3 frameshift

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 4.15
Variant links:
Genes affected
PINK1 (HGNC:14581): (PTEN induced kinase 1) This gene encodes a serine/threonine protein kinase that localizes to mitochondria. It is thought to protect cells from stress-induced mitochondrial dysfunction. Mutations in this gene cause one form of autosomal recessive early-onset Parkinson disease. [provided by RefSeq, Jul 2008]
PINK1-AS (HGNC:38872): (PINK1 antisense RNA)

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PVS1
?
    PVS1 - null variant (nonsense, frameshift, canonical ±1 or 2 splice sites, initiation codon, single or multiexon deletion) in a gene where LOF is a known mechanism of disease
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.103 CDS is truncated, and there are 3 pathogenic variants in the truncated region.
PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
PP5
?
    PP5 - Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-20650512-A-AAGTT is Pathogenic according to our data. Variant chr1-20650512-A-AAGTT is described in ClinVar as [Pathogenic]. Clinvar id is 2409.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PINK1NM_032409.3 linkuse as main transcriptc.1570_1573dup p.Asp525ValfsTer38 frameshift_variant 8/8 ENST00000321556.5
PINK1-ASNR_046507.1 linkuse as main transcriptn.1681_1682insAACT non_coding_transcript_exon_variant 1/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PINK1ENST00000321556.5 linkuse as main transcriptc.1570_1573dup p.Asp525ValfsTer38 frameshift_variant 8/81 NM_032409.3 P1Q9BXM7-1
PINK1-ASENST00000451424.1 linkuse as main transcriptn.1681_1682insAACT non_coding_transcript_exon_variant 1/32
PINK1ENST00000400490.2 linkuse as main transcriptn.663_666dup non_coding_transcript_exon_variant 4/42
PINK1ENST00000492302.1 linkuse as main transcriptn.3020_3023dup non_coding_transcript_exon_variant 5/52

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
Cov.:
33
GnomAD4 exome
Cov.:
38
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
Cov.:
33

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Autosomal recessive early-onset Parkinson disease 6 Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMSep 01, 2004- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs730880302; hg19: chr1-20977005; API