Genetic Variant NM_007262.5:c.-24+75_-24+92delTGTGCTGGACGGTGTCCC (chr1-7961850-GGTGCTGGACGGTGTCCCT-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_007262.5(PARK7):c.-24+75_-24+92delTGTGCTGGACGGTGTCCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,158 control chromosomes in the GnomAD database, including 1,911 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.14 ( 1911 hom., cov: 30)

Exomes 𝑓: 0.026 ( 0 hom. )

Consequence

PARK7
NM_007262.5 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.721

Publications

7 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 1-7961850-GGTGCTGGACGGTGTCCCT-G is Benign according to our data. Variant chr1-7961850-GGTGCTGGACGGTGTCCCT-G is described in ClinVar as Benign. ClinVar VariationId is 1246972.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
PARK7	NM_007262.5 link	c.-24+75_-24+92delTGTGCTGGACGGTGTCCC	intron_variant	Intron 1 of 6	ENST00000338639.10	NP_009193.2
PARK7	XM_005263424.4 link	c.-237_-220delTGTGCTGGACGGTGTCCC	5_prime_UTR_variant	Exon 1 of 7		XP_005263481.1
PARK7	NM_001123377.2 link	c.-24+133_-24+150delTGTGCTGGACGGTGTCCC	intron_variant	Intron 1 of 6		NP_001116849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARK7	ENST00000338639.10 link	c.-24+58_-24+75delGTGCTGGACGGTGTCCCT		intron_variant	Intron 1 of 6	1	NM_007262.5	ENSP00000340278.5

Frequencies

GnomAD3 genomes

AF:

0.140

AC:

21183

AN:

151770

Hom.:

1909

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0470

Gnomad AMI

AF:

0.0451

Gnomad AMR

AF:

0.113

Gnomad ASJ

AF:

0.114

Gnomad EAS

AF:

0.0640

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.316

Gnomad MID

AF:

0.0955

Gnomad NFE

AF:

0.186

Gnomad OTH

AF:

0.129

GnomAD4 exome

AF:

0.0257

AC:

AN:

272

Hom.:

AF XY:

0.0275

AC XY:

AN XY:

182

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0330

AC:

AN:

212

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.139

AC:

21179

AN:

151886

Hom.:

1911

Cov.:

AF XY:

0.142

AC XY:

10547

AN XY:

74220

show subpopulations

African (AFR)

AF:

0.0469

AC:

1943

AN:

41436

American (AMR)

AF:

0.113

AC:

1730

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.114

AC:

397

AN:

3472

East Asian (EAS)

AF:

0.0638

AC:

329

AN:

5156

South Asian (SAS)

AF:

0.101

AC:

489

AN:

4818

European-Finnish (FIN)

AF:

0.316

AC:

3323

AN:

10522

Middle Eastern (MID)

AF:

0.103

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.186

AC:

12627

AN:

67890

Other (OTH)

AF:

0.128

AC:

270

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

796

1592

2389

3185

3981

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

234

468

702

936

1170

<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:

0.0742

Hom.:

105

Bravo

AF:

0.123

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Oct 04, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.72

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over