Genetic Variant PARK7:c.410-2128G>T (chr1-7982766-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007262.5(PARK7):c.410-2128G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,090 control chromosomes in the GnomAD database, including 5,656 homozygotes. 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: 𝑓 0.25 ( 5656 hom., cov: 32)

Exomes 𝑓: 0.13 ( 0 hom. )

Consequence

PARK7
NM_007262.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0860

Publications

22 publications found

Variant links:

Genes affected

PARK7 (HGNC:16369): (Parkinsonism associated deglycase) The product of this gene belongs to the peptidase C56 family of proteins. It acts as a positive regulator of androgen receptor-dependent transcription. It may also function as a redox-sensitive chaperone, as a sensor for oxidative stress, and it apparently protects neurons against oxidative stress and cell death. Defects in this gene are the cause of autosomal recessive early-onset Parkinson disease 7. Two transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Jul 2008]

PARK7 Gene-Disease associations (from GenCC):

Parkinson disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
autosomal recessive early-onset Parkinson disease 7
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics
young-onset Parkinson disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PARK7 links:

Y_RNA (HGNC:):

Y_RNA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
PARK7	NM_007262.5 link	c.410-2128G>T	intron_variant	Intron 6 of 6	ENST00000338639.10	NP_009193.2
PARK7	NM_001123377.2 link	c.410-2128G>T	intron_variant	Intron 6 of 6		NP_001116849.1
PARK7	XM_005263424.4 link	c.410-2128G>T	intron_variant	Intron 6 of 6		XP_005263481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARK7	ENST00000338639.10 link	c.410-2128G>T		intron_variant	Intron 6 of 6	1	NM_007262.5	ENSP00000340278.5

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

38016

AN:

151964

Hom.:

5646

Cov.:

show subpopulations

Gnomad AFR

AF:

0.312

Gnomad AMI

AF:

0.0746

Gnomad AMR

AF:

0.347

Gnomad ASJ

AF:

0.121

Gnomad EAS

AF:

0.629

Gnomad SAS

AF:

0.135

Gnomad FIN

AF:

0.293

Gnomad MID

AF:

0.0924

Gnomad NFE

AF:

0.174

Gnomad OTH

AF:

0.219

GnomAD4 exome

AF:

0.125

AC:

AN:

Hom.:

AF XY:

0.250

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.250

AC:

38063

AN:

152082

Hom.:

5656

Cov.:

AF XY:

0.256

AC XY:

19045

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.312

AC:

12931

AN:

41470

American (AMR)

AF:

0.348

AC:

5314

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.121

AC:

419

AN:

3468

East Asian (EAS)

AF:

0.628

AC:

3248

AN:

5168

South Asian (SAS)

AF:

0.134

AC:

647

AN:

4828

European-Finnish (FIN)

AF:

0.293

AC:

3099

AN:

10576

Middle Eastern (MID)

AF:

0.0993

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.174

AC:

11846

AN:

67986

Other (OTH)

AF:

0.219

AC:

462

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1402

2803

4205

5606

7008

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

378

756

1134

1512

1890

<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:

0.194

Hom.:

6107

Bravo

AF:

0.266

Asia WGS

AF:

0.373

AC:

1296

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

9.6

(source)

DANN

Benign

0.61

PhyloP100

0.086

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

Computational scores

Splicing

Publications

Other links and lift over