chr2-156326699-TC-T

Variant names:

• chr2-156326699-TC-T
• rs35479735
• NM_006186.4:c.1361+18delG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_006186.4(NR4A2):​c.1361+18delG variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.79 (47833 hom., cov: 0)
  • Exomes 𝑓: 0.77 (432389 hom.)
• Consequence: NR4A2 NM_006186.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.439
• Publications: 17 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.891 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR4A2	NM_006186.4	MANE Select	c.1361+18delG		intron	N/A	NP_006177.1	F1D8N6
	NR4A2	NM_173173.3		c.1172+18delG		intron	N/A	NP_775265.1	P43354-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR4A2	ENST00000339562.9	TSL:1 MANE Select	c.1361+18delG		intron	N/A	ENSP00000344479.4	P43354-1
	NR4A2	ENST00000426264.5	TSL:1	c.1172+18delG		intron	N/A	ENSP00000389986.1	P43354-2
	NR4A2	ENST00000409572.5	TSL:5	c.1361+18delG		intron	N/A	ENSP00000386747.1	P43354-1

Frequencies

GnomAD3 genomes AF: 0.786 AC: 119455 AN: 151962 Hom.: 47783 Cov.: 0

Gnomad AFR AF: 0.899

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.678

Gnomad FIN AF: 0.785

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.783

Gnomad OTH AF: 0.787

GnomAD2 exomes AF: 0.715 AC: 177720 AN: 248568 AF XY: 0.721

Gnomad AFR exome AF: 0.899

Gnomad AMR exome AF: 0.509

Gnomad ASJ exome AF: 0.782

Gnomad EAS exome AF: 0.434

Gnomad FIN exome AF: 0.793

Gnomad NFE exome AF: 0.785

Gnomad OTH exome AF: 0.750

GnomAD4 exome AF: 0.766 AC: 1117687 AN: 1459912 Hom.: 432389 Cov.: 0 AF XY: 0.763 AC XY: 554559 AN XY: 726338

African (AFR) AF: 0.906 AC: 30308 AN: 33452

American (AMR) AF: 0.524 AC: 23445 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.789 AC: 20624 AN: 26130

East Asian (EAS) AF: 0.456 AC: 18098 AN: 39692

South Asian (SAS) AF: 0.683 AC: 58855 AN: 86206

European-Finnish (FIN) AF: 0.798 AC: 42429 AN: 53138

Middle Eastern (MID) AF: 0.727 AC: 4188 AN: 5758

European-Non Finnish (NFE) AF: 0.787 AC: 873800 AN: 1110504

Other (OTH) AF: 0.762 AC: 45940 AN: 60312

GnomAD4 genome AF: 0.786 AC: 119556 AN: 152080 Hom.: 47833 Cov.: 0 AF XY: 0.780 AC XY: 57999 AN XY: 74328

African (AFR) AF: 0.899 AC: 37291 AN: 41482

American (AMR) AF: 0.650 AC: 9923 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.781 AC: 2712 AN: 3472

East Asian (EAS) AF: 0.439 AC: 2268 AN: 5162

South Asian (SAS) AF: 0.679 AC: 3268 AN: 4814

European-Finnish (FIN) AF: 0.785 AC: 8305 AN: 10574

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.783 AC: 53223 AN: 67988

Other (OTH) AF: 0.787 AC: 1658 AN: 2108

Alfa AF: 0.790 Hom.: 8647

Bravo AF: 0.776

Asia WGS AF: 0.625 AC: 2175 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.44
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: rs35479735; hg19: chr2-157183211; COSMIC: COSV104413237; COSMIC: COSV104413237;