2-156325324-CTG-C

Variant names:

• chr2-156325324-CTG-C
• rs3832066
• NM_006186.4:c.*418_*419delCA

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

NR4A2 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006186.4. 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
	NR4A2	NM_006186.4	MANE Select	c.*418_*419delCA		3_prime_UTR	Exon 8 of 8	NP_006177.1
	NR4A2	NM_173173.3		c.*418_*419delCA		3_prime_UTR	Exon 8 of 8	NP_775265.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR4A2	ENST00000339562.9	TSL:1 MANE Select	c.*418_*419delCA		3_prime_UTR	Exon 8 of 8	ENSP00000344479.4
	NR4A2	ENST00000426264.5	TSL:1	c.*418_*419delCA		3_prime_UTR	Exon 8 of 8	ENSP00000389986.1
	NR4A2	ENST00000417764.5	TSL:5	n.*726_*727delCA		non_coding_transcript_exon	Exon 7 of 7	ENSP00000415632.1

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

African (AFR) AF: 0.349 AC: 780 AN: 2236

American (AMR) AF: 0.392 AC: 1271 AN: 3246

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 745 AN: 1640

East Asian (EAS) AF: 0.286 AC: 1015 AN: 3546

South Asian (SAS) AF: 0.413 AC: 4204 AN: 10190

European-Finnish (FIN) AF: 0.485 AC: 1371 AN: 2826

Middle Eastern (MID) AF: 0.455 AC: 122 AN: 268

European-Non Finnish (NFE) AF: 0.470 AC: 18377 AN: 39132

Other (OTH) AF: 0.449 AC: 1553 AN: 3460

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

African (AFR) AF: 0.295 AC: 12098 AN: 40972

American (AMR) AF: 0.344 AC: 5182 AN: 15076

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 1803 AN: 3458

East Asian (EAS) AF: 0.179 AC: 920 AN: 5128

South Asian (SAS) AF: 0.438 AC: 2084 AN: 4762

European-Finnish (FIN) AF: 0.551 AC: 5604 AN: 10174

Middle Eastern (MID) AF: 0.459 AC: 134 AN: 292

European-Non Finnish (NFE) AF: 0.545 AC: 36761 AN: 67478

Other (OTH) AF: 0.447 AC: 935 AN: 2092

Alfa AF: 0.339 Hom.: 913

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

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
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: rs3832066; hg19: chr2-157181836;