Variant 2-156325413-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006186.4(NR4A2):c.*331T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 363,146 control chromosomes in the GnomAD database, including 39,694 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 14020 hom., cov: 32)

Exomes 𝑓: 0.48 ( 25674 hom. )

Consequence

NR4A2
NM_006186.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.90

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 2-156325413-A-C is Benign according to our data. Variant chr2-156325413-A-C is described in ClinVar as [Benign]. Clinvar id is 331655.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR4A2	NM_006186.4 linkuse as main transcript	c.*331T>G		3_prime_UTR_variant	8/8	ENST00000339562.9	NP_006177.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR4A2	ENST00000339562.9 linkuse as main transcript	c.*331T>G		3_prime_UTR_variant	8/8	1	NM_006186.4	ENSP00000344479	P1	P43354-1

Frequencies

GnomAD3 genomes

AF:

0.394

AC:

59795

AN:

151894

Hom.:

14022

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.503

Gnomad AMR

AF:

0.317

Gnomad ASJ

AF:

0.476

Gnomad EAS

AF:

0.176

Gnomad SAS

AF:

0.435

Gnomad FIN

AF:

0.552

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.536

Gnomad OTH

AF:

0.402

GnomAD4 exome

AF:

0.478

AC:

100910

AN:

211132

Hom.:

25674

Cov.:

AF XY:

0.473

AC XY:

54439

AN XY:

115038

show subpopulations

Gnomad4 AFR exome

AF:

0.152

Gnomad4 AMR exome

AF:

0.283

Gnomad4 ASJ exome

AF:

0.475

Gnomad4 EAS exome

AF:

0.170

Gnomad4 SAS exome

AF:

0.442

Gnomad4 FIN exome

AF:

0.559

Gnomad4 NFE exome

AF:

0.539

Gnomad4 OTH exome

AF:

0.483

GnomAD4 genome

AF:

0.393

AC:

59779

AN:

152014

Hom.:

14020

Cov.:

AF XY:

0.389

AC XY:

28903

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.159

Gnomad4 AMR

AF:

0.317

Gnomad4 ASJ

AF:

0.476

Gnomad4 EAS

AF:

0.177

Gnomad4 SAS

AF:

0.436

Gnomad4 FIN

AF:

0.552

Gnomad4 NFE

AF:

0.536

Gnomad4 OTH

AF:

0.399

Alfa

AF:

0.490

Hom.:

18229

Bravo

AF:

0.358

Asia WGS

AF:

0.290

AC:

1009

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Parkinson disease, late-onset

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over