rs34884856

Positions:

• chr2-156333105-T-TG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000409572.5(NR4A2):​c.-126-2315_-126-2314insC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.72 (40022 hom., cov: 0)
• Consequence: NR4A2 ENST00000409572.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.478

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.

• BP6: Variant 2-156333105-T-TG is Benign according to our data. Variant chr2-156333105-T-TG is described in ClinVar as [Benign]. Clinvar id is 1233991.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR4A2	ENST00000409572.5	c.-126-2315_-126-2314insC		intron_variant		5		ENSP00000386747	P1

Frequencies

GnomAD3 genomes AF: 0.721 AC: 109439 AN: 151748 Hom.: 40010 Cov.: 0

Gnomad AFR AF: 0.676

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.619

Gnomad ASJ AF: 0.774

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.694

Gnomad NFE AF: 0.783

Gnomad OTH AF: 0.730

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

GnomAD4 genome AF: 0.721 AC: 109488 AN: 151862 Hom.: 40022 Cov.: 0 AF XY: 0.718 AC XY: 53285 AN XY: 74244

Gnomad4 AFR AF: 0.676

Gnomad4 AMR AF: 0.618

Gnomad4 ASJ AF: 0.774

Gnomad4 EAS AF: 0.436

Gnomad4 SAS AF: 0.671

Gnomad4 FIN AF: 0.788

Gnomad4 NFE AF: 0.783

Gnomad4 OTH AF: 0.730

Alfa AF: 0.736 Hom.: 3793

Bravo AF: 0.695

Asia WGS AF: 0.600 AC: 2086 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 19, 2019

This variant is associated with the following publications: (PMID: 15635701) -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs34884856; hg19: chr2-157189617;