1-7969434-T-G

Variant names:

• chr1-7969434-T-G
• rs2641116
• NM_007262.5:c.252+30T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_007262.5(PARK7):​c.252+30T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 910,904 control chromosomes in the GnomAD database, including 39,439 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (4959 hom., cov: 31)
  • Exomes 𝑓: 0.34 (34480 hom.)
• Consequence: PARK7 NM_007262.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.194
• Publications: 16 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-7969434-T-G is Benign according to our data. Variant chr1-7969434-T-G is described in ClinVar as Benign. ClinVar VariationId is 1227164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007262.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARK7	NM_007262.5	MANE Select	c.252+30T>G		intron	N/A	NP_009193.2
	PARK7	NM_001123377.2		c.252+30T>G		intron	N/A	NP_001116849.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARK7	ENST00000338639.10	TSL:1 MANE Select	c.252+30T>G		intron	N/A	ENSP00000340278.5
	PARK7	ENST00000493678.5	TSL:1	c.252+30T>G		intron	N/A	ENSP00000418770.1
	PARK7	ENST00000377488.5	TSL:3	c.252+30T>G		intron	N/A	ENSP00000366708.1

Frequencies

GnomAD3 genomes AF: 0.256 AC: 35203 AN: 137702 Hom.: 4948 Cov.: 31

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.0674

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.0922

Gnomad EAS AF: 0.653

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.0935

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.220

GnomAD2 exomes AF: 0.264 AC: 61778 AN: 233574 AF XY: 0.243

Gnomad AFR exome AF: 0.305

Gnomad AMR exome AF: 0.486

Gnomad ASJ exome AF: 0.0894

Gnomad EAS exome AF: 0.641

Gnomad FIN exome AF: 0.296

Gnomad NFE exome AF: 0.177

Gnomad OTH exome AF: 0.211

GnomAD4 exome AF: 0.336 AC: 259416 AN: 773052 Hom.: 34480 Cov.: 17 AF XY: 0.315 AC XY: 126405 AN XY: 401878

African (AFR) AF: 0.301 AC: 8529 AN: 28338

American (AMR) AF: 0.495 AC: 20348 AN: 41134

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 2097 AN: 14960

East Asian (EAS) AF: 0.673 AC: 23771 AN: 35344

South Asian (SAS) AF: 0.131 AC: 9198 AN: 70330

European-Finnish (FIN) AF: 0.349 AC: 14927 AN: 42764

Middle Eastern (MID) AF: 0.117 AC: 365 AN: 3120

European-Non Finnish (NFE) AF: 0.336 AC: 169095 AN: 503444

Other (OTH) AF: 0.330 AC: 11086 AN: 33618

GnomAD4 genome AF: 0.256 AC: 35252 AN: 137852 Hom.: 4959 Cov.: 31 AF XY: 0.266 AC XY: 17764 AN XY: 66716

African (AFR) AF: 0.316 AC: 10992 AN: 34742

American (AMR) AF: 0.352 AC: 5063 AN: 14378

Ashkenazi Jewish (ASJ) AF: 0.0922 AC: 302 AN: 3274

East Asian (EAS) AF: 0.653 AC: 3238 AN: 4960

South Asian (SAS) AF: 0.156 AC: 604 AN: 3868

European-Finnish (FIN) AF: 0.341 AC: 3103 AN: 9110

Middle Eastern (MID) AF: 0.0985 AC: 26 AN: 264

European-Non Finnish (NFE) AF: 0.177 AC: 11437 AN: 64444

Other (OTH) AF: 0.220 AC: 429 AN: 1952

Alfa AF: 0.172 Hom.: 890

Bravo AF: 0.246

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.36
DANN	Benign	0.71
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2641116; hg19: chr1-8029494; COSMIC: COSV58579960;