chr2-156331633-C-T

Variant names:

• chr2-156331633-C-T
• rs834835
• NM_006186.4:c.-126-842G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006186.4(NR4A2):​c.-126-842G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 152,112 control chromosomes in the GnomAD database, including 27,472 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.58 (27472 hom., cov: 32)
• Consequence: NR4A2 NM_006186.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.113

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR4A2	NM_006186.4	c.-126-842G>A		intron_variant	Intron 1 of 7	ENST00000339562.9	NP_006177.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR4A2	ENST00000339562.9	c.-126-842G>A		intron_variant	Intron 1 of 7	1	NM_006186.4	ENSP00000344479.4

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88134 AN: 151996 Hom.: 27464 Cov.: 32

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.724

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.620

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.580 AC: 88152 AN: 152112 Hom.: 27472 Cov.: 32 AF XY: 0.580 AC XY: 43131 AN XY: 74334

Gnomad4 AFR AF: 0.355

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.739

Gnomad4 EAS AF: 0.435

Gnomad4 SAS AF: 0.601

Gnomad4 FIN AF: 0.724

Gnomad4 NFE AF: 0.705

Gnomad4 OTH AF: 0.621

Alfa AF: 0.672 Hom.: 32298

Bravo AF: 0.547

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	12
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs834835; hg19: chr2-157188145;