Genetic Variant NR4A2:c.-126-2315_-126-2314insC (chr2-156333105-T-TG) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The ENST00000871392.1(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
ENST00000871392.1 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.478

Publications

5 publications found

Variant links:

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

NR4A2 links:

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new If you want to explore the variant's impact on the transcript ENST00000871392.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000871392.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NR4A2	ENST00000409572.5	TSL:5	c.-126-2315_-126-2314insC	intron	N/A	ENSP00000386747.1	P43354-1
NR4A2	ENST00000871392.1		c.-126-2315_-126-2314insC	intron	N/A	ENSP00000541451.1
NR4A2	ENST00000944325.1		c.-127+1318_-127+1319insC	intron	N/A	ENSP00000614384.1

Frequencies

GnomAD3 genomes

AF:

0.721

AC:

109439

AN:

151748

Hom.:

40010

Cov.:

show subpopulations

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.:

AF XY:

0.718

AC XY:

53285

AN XY:

74244

show subpopulations

African (AFR)

AF:

0.676

AC:

28008

AN:

41458

American (AMR)

AF:

0.618

AC:

9447

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.774

AC:

2685

AN:

3468

East Asian (EAS)

AF:

0.436

AC:

2224

AN:

5104

South Asian (SAS)

AF:

0.671

AC:

3225

AN:

4806

European-Finnish (FIN)

AF:

0.788

AC:

8322

AN:

10566

Middle Eastern (MID)

AF:

0.685

AC:

200

AN:

292

European-Non Finnish (NFE)

AF:

0.783

AC:

53129

AN:

67866

Other (OTH)

AF:

0.730

AC:

1544

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1503

3007

4510

6014

7517

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

830

1660

2490

3320

4150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.751

Hom.:

5248

Bravo

AF:

0.695

Asia WGS

AF:

0.600

AC:

2086

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.48

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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2-156333105-TG-TGG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over