rs2641117

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
PARK7	NM_007262.5	c.252+46G>A		intron_variant		ENST00000338639.10	NP_009193.2
PARK7	NM_001123377.2	c.252+46G>A		intron_variant			NP_001116849.1
PARK7	XM_005263424.4	c.252+46G>A		intron_variant			XP_005263481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARK7	ENST00000338639.10	c.252+46G>A		intron_variant		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

GnomAD3 exomes AF: 0.294 AC: 63677 AN: 216602 Hom.: 13791 AF XY: 0.265 AC XY: 31111 AN XY: 117360

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 SAS exome AF: 0.116

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

Gnomad4 AFR exome AF: 0.816

Gnomad4 AMR exome AF: 0.520

Gnomad4 ASJ exome AF: 0.136

Gnomad4 EAS exome AF: 0.665

Gnomad4 SAS exome AF: 0.132

Gnomad4 FIN exome AF: 0.343

Gnomad4 NFE exome AF: 0.318

Gnomad4 OTH exome AF: 0.365

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

Gnomad4 AFR AF: 0.751

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.0935

Gnomad4 EAS AF: 0.652

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.351

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.323

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.025
DANN	Benign	0.51

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

LitVar

Other links and lift over

dbSNP: rs2641117; hg19: chr1-8029510;