rs2298298

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032409.3(PINK1):c.388-7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.869 in 1,613,594 control chromosomes in the GnomAD database, including 610,562 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.84 ( 53986 hom., cov: 31)

Exomes 𝑓: 0.87 ( 556576 hom. )

Consequence

PINK1
NM_032409.3 splice_region, intron

Scores

Splicing: ADA: 0.00005242

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.271

Publications

26 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive early-onset Parkinson disease 6
Inheritance: AD, AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
Parkinson disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
young-onset Parkinson disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PINK1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 1-20637835-A-G is Benign according to our data. Variant chr1-20637835-A-G is described in ClinVar as Benign. ClinVar VariationId is 262027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PINK1	NM_032409.3 link	c.388-7A>G		splice_region_variant, intron_variant	Intron 1 of 7	ENST00000321556.5	NP_115785.1	Q9BXM7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PINK1	ENST00000321556.5 link	c.388-7A>G		splice_region_variant, intron_variant	Intron 1 of 7	1	NM_032409.3	ENSP00000364204.3		Q9BXM7-1

Frequencies

GnomAD3 genomes

AF:

0.840

AC:

127756

AN:

152014

Hom.:

53957

Cov.:

show subpopulations

Gnomad AFR

AF:

0.762

Gnomad AMI

AF:

0.837

Gnomad AMR

AF:

0.809

Gnomad ASJ

AF:

0.903

Gnomad EAS

AF:

0.797

Gnomad SAS

AF:

0.881

Gnomad FIN

AF:

0.927

Gnomad MID

AF:

0.902

Gnomad NFE

AF:

0.878

Gnomad OTH

AF:

0.864

GnomAD2 exomes

AF:

0.862

AC:

216056

AN:

250728

AF XY:

0.867

show subpopulations

Gnomad AFR exome

AF:

0.764

Gnomad AMR exome

AF:

0.809

Gnomad ASJ exome

AF:

0.900

Gnomad EAS exome

AF:

0.811

Gnomad FIN exome

AF:

0.929

Gnomad NFE exome

AF:

0.877

Gnomad OTH exome

AF:

0.871

GnomAD4 exome

AF:

0.872

AC:

1274335

AN:

1461462

Hom.:

556576

Cov.:

AF XY:

0.873

AC XY:

634662

AN XY:

727044

show subpopulations

African (AFR)

AF:

0.752

AC:

25177

AN:

33460

American (AMR)

AF:

0.807

AC:

36091

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.900

AC:

23532

AN:

26136

East Asian (EAS)

AF:

0.791

AC:

31394

AN:

39700

South Asian (SAS)

AF:

0.882

AC:

76010

AN:

86226

European-Finnish (FIN)

AF:

0.927

AC:

49516

AN:

53416

Middle Eastern (MID)

AF:

0.911

AC:

5015

AN:

5504

European-Non Finnish (NFE)

AF:

0.877

AC:

975166

AN:

1111926

Other (OTH)

AF:

0.869

AC:

52434

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

9946

19892

29838

39784

49730

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21310

42620

63930

85240

106550

<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

AF:

0.840

AC:

127840

AN:

152132

Hom.:

53986

Cov.:

AF XY:

0.843

AC XY:

62669

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.762

AC:

31600

AN:

41464

American (AMR)

AF:

0.808

AC:

12349

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.903

AC:

3134

AN:

3472

East Asian (EAS)

AF:

0.796

AC:

4117

AN:

5170

South Asian (SAS)

AF:

0.881

AC:

4247

AN:

4820

European-Finnish (FIN)

AF:

0.927

AC:

9822

AN:

10594

Middle Eastern (MID)

AF:

0.898

AC:

264

AN:

294

European-Non Finnish (NFE)

AF:

0.878

AC:

59719

AN:

68012

Other (OTH)

AF:

0.865

AC:

1826

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1058

2115

3173

4230

5288

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

890

1780

2670

3560

4450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.862

Hom.:

67148

Bravo

AF:

0.829

Asia WGS

AF:

0.821

AC:

2856

AN:

3478

EpiCase

AF:

0.880

EpiControl

AF:

0.883

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Jul 31, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 95% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 88. Only high quality variants are reported. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Mar 08, 2019

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 05, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal recessive early-onset Parkinson disease 6

Benign:3

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.0

(source)

DANN

Benign

0.55

PhyloP100

-0.27

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000052

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over