rs200968609

Variant names:

• chr1-7961850-GGTGCTGGACGGTGTCCCT-G
• rs200968609
• NM_007262.5:c.-24+75_-24+92delTGTGCTGGACGGTGTCCC

Your query was ambiguous. Multiple possible variants found:

• chr1-7961850-GGTGCTGGACGGTGTCCCT-G
• chr1-7961850-GGTGCTGGACGGTGTCCCT-GGTGCTGGACGGTGTCCCTGTGCTGGACGGTGTCCCT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.721
• Publications: 7 publications found

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

ACMG classification

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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARK7	NM_007262.5	c.-24+75_-24+92delTGTGCTGGACGGTGTCCC		intron_variant	Intron 1 of 6	ENST00000338639.10	NP_009193.2
PARK7	XM_005263424.4	c.-237_-220delTGTGCTGGACGGTGTCCC		5_prime_UTR_variant	Exon 1 of 7		XP_005263481.1
PARK7	NM_001123377.2	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	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.: 30

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: 7 AN: 272 Hom.: 0 AF XY: 0.0275 AC XY: 5 AN XY: 182

African (AFR) AF: 0.00 AC: 0 AN: 6

American (AMR) AF: 0.00 AC: 0 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 10

South Asian (SAS) AF: 0.00 AC: 0 AN: 16

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0330 AC: 7 AN: 212

Other (OTH) AF: 0.00 AC: 0 AN: 14

GnomAD4 genome AF: 0.139 AC: 21179 AN: 151886 Hom.: 1911 Cov.: 30 AF XY: 0.142 AC XY: 10547 AN XY: 74220

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: 30 AN: 292

European-Non Finnish (NFE) AF: 0.186 AC: 12627 AN: 67890

Other (OTH) AF: 0.128 AC: 270 AN: 2108

Alfa AF: 0.0742 Hom.: 105

Bravo AF: 0.123

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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)

Splicing

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

Other links and lift over

dbSNP: rs200968609; hg19: chr1-8021910; COSMIC: COSV58580448; COSMIC: COSV58580448;