2-156325324-CTG-C

Position:

• chr2-156325324-CTG-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_006186.4(NR4A2):​c.*418_*419delCA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 216,878 control chromosomes in the GnomAD database, including 18,725 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.44 (15514 hom., cov: 0)
  • Exomes 𝑓: 0.44 (3211 hom.)
• Consequence: NR4A2 NM_006186.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.22

Genes affected

NR4A2 (HGNC:7981): (nuclear receptor subfamily 4 group A member 2) This gene encodes a member of the steroid-thyroid hormone-retinoid receptor superfamily. The encoded protein may act as a transcription factor. Mutations in this gene have been associated with disorders related to dopaminergic dysfunction, including Parkinson disease, schizophernia, and manic depression. Misregulation of this gene may be associated with rheumatoid arthritis. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-156325324-CTG-C is Benign according to our data. Variant chr2-156325324-CTG-C is described in ClinVar as [Benign]. Clinvar id is 331653.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR4A2	NM_006186.4	c.*418_*419delCA		3_prime_UTR_variant	8/8	ENST00000339562.9	NP_006177.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR4A2	ENST00000339562	c.*418_*419delCA		3_prime_UTR_variant	8/8	1	NM_006186.4	ENSP00000344479.4

Frequencies

GnomAD3 genomes AF: 0.439 AC: 65975 AN: 150230 Hom.: 15510 Cov.: 0

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.506

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.471

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.450

GnomAD4 exome AF: 0.442 AC: 29438 AN: 66544 Hom.: 3211 AF XY: 0.436 AC XY: 15371 AN XY: 35244

Gnomad4 AFR exome AF: 0.349

Gnomad4 AMR exome AF: 0.392

Gnomad4 ASJ exome AF: 0.454

Gnomad4 EAS exome AF: 0.286

Gnomad4 SAS exome AF: 0.413

Gnomad4 FIN exome AF: 0.485

Gnomad4 NFE exome AF: 0.470

Gnomad4 OTH exome AF: 0.449

GnomAD4 genome AF: 0.439 AC: 65977 AN: 150334 Hom.: 15514 Cov.: 0 AF XY: 0.435 AC XY: 31884 AN XY: 73352

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.521

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.551

Gnomad4 NFE AF: 0.545

Gnomad4 OTH AF: 0.447

Bravo AF: 0.409

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Parkinson Disease, Dominant/Recessive Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs3832066; hg19: chr2-157181836;