rs13428968

chr2-156336101-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000409572.5(NR4A2):c.-126-5310A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,258 control chromosomes in the GnomAD database, including 1,681 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 0.14 (1681 hom., cov: 33)
• Consequence: NR4A2 ENST00000409572.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.84

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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR4A2	ENST00000409572.5	c.-126-5310A>G		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20818 AN: 152140 Hom.: 1676 Cov.: 33

Gnomad AFR AF: 0.0492

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.137 AC: 20832 AN: 152258 Hom.: 1681 Cov.: 33 AF XY: 0.142 AC XY: 10557 AN XY: 74430

Gnomad4 AFR AF: 0.0492

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.261

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.174

Alfa AF: 0.134 Hom.: 158

Bravo AF: 0.132

Asia WGS AF: 0.250 AC: 872 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
Cadd	Benign	21
Dann	Benign	0.84

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs13428968; hg19: chr2-157192613;