rs2641117

Variant names:

• chr1-7969450-G-A
• rs2641117
• NM_007262.5:c.252+46G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-7969450-G-A
• chr1-7969450-G-C
• chr1-7969450-G-T

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+46G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 143,474 control chromosomes in the GnomAD database, including 15,384 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (15384 hom., cov: 29)
  • Exomes 𝑓: 0.35 (42374 hom.)
  • Failed GnomAD Quality Control
• Consequence: PARK7 NM_007262.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.75
• Publications: 3 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=-0.82).
• BP6: Variant 1-7969450-G-A is Benign according to our data. Variant chr1-7969450-G-A is described in ClinVar as Benign. ClinVar VariationId is 1275885.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARK7	NM_007262.5	c.252+46G>A		intron_variant	Intron 4 of 6	ENST00000338639.10	NP_009193.2
PARK7	NM_001123377.2	c.252+46G>A		intron_variant	Intron 4 of 6		NP_001116849.1
PARK7	XM_005263424.4	c.252+46G>A		intron_variant	Intron 4 of 6		XP_005263481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARK7	ENST00000338639.10	c.252+46G>A		intron_variant	Intron 4 of 6	1	NM_007262.5	ENSP00000340278.5

Frequencies

GnomAD3 genomes AF: 0.391 AC: 56071 AN: 143332 Hom.: 15339 Cov.: 29

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.0692

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.0935

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.132

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.324

GnomAD2 exomes AF: 0.294 AC: 63677 AN: 216602 AF XY: 0.265

Gnomad AFR exome AF: 0.759

Gnomad AMR exome AF: 0.507

Gnomad ASJ exome AF: 0.0972

Gnomad EAS exome AF: 0.636

Gnomad FIN exome AF: 0.288

Gnomad NFE exome AF: 0.171

Gnomad OTH exome AF: 0.235

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.350 AC: 208751 AN: 596486 Hom.: 42374 Cov.: 10 AF XY: 0.323 AC XY: 103078 AN XY: 319606

African (AFR) AF: 0.816 AC: 19828 AN: 24294

American (AMR) AF: 0.520 AC: 20161 AN: 38778

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 1928 AN: 14142

East Asian (EAS) AF: 0.665 AC: 22727 AN: 34170

South Asian (SAS) AF: 0.132 AC: 8481 AN: 64460

European-Finnish (FIN) AF: 0.343 AC: 14675 AN: 42784

Middle Eastern (MID) AF: 0.160 AC: 497 AN: 3100

European-Non Finnish (NFE) AF: 0.318 AC: 110049 AN: 346272

Other (OTH) AF: 0.365 AC: 10405 AN: 28486

GnomAD4 genome AF: 0.392 AC: 56178 AN: 143474 Hom.: 15384 Cov.: 29 AF XY: 0.399 AC XY: 27660 AN XY: 69332

African (AFR) AF: 0.751 AC: 30685 AN: 40870

American (AMR) AF: 0.408 AC: 5893 AN: 14436

Ashkenazi Jewish (ASJ) AF: 0.0935 AC: 306 AN: 3272

East Asian (EAS) AF: 0.652 AC: 3209 AN: 4922

South Asian (SAS) AF: 0.162 AC: 637 AN: 3922

European-Finnish (FIN) AF: 0.351 AC: 3085 AN: 8792

Middle Eastern (MID) AF: 0.143 AC: 38 AN: 266

European-Non Finnish (NFE) AF: 0.181 AC: 11614 AN: 64136

Other (OTH) AF: 0.323 AC: 653 AN: 2020

Alfa AF: 0.125 Hom.: 329

Bravo AF: 0.405

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.025
DANN	Benign	0.51
PhyloP100		-1.7
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: rs2641117; hg19: chr1-8029510;