rs13428968

Variant names:

• chr2-156336101-T-C
• rs13428968
• ENST00000409572.5:c.-126-5310A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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.

• 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR4A2	ENST00000409572.5	c.-126-5310A>G		intron_variant	Intron 1 of 7	5		ENSP00000386747.1

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

African (AFR) AF: 0.0492 AC: 2043 AN: 41566

American (AMR) AF: 0.178 AC: 2727 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 760 AN: 3468

East Asian (EAS) AF: 0.261 AC: 1352 AN: 5180

South Asian (SAS) AF: 0.173 AC: 834 AN: 4830

European-Finnish (FIN) AF: 0.168 AC: 1775 AN: 10592

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10770 AN: 68000

Other (OTH) AF: 0.174 AC: 368 AN: 2112

Alfa AF: 0.151 Hom.: 3938

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
PhyloP100		2.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs13428968; hg19: chr2-157192613;