Variant 2-156325392-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_006186.4(NR4A2):c.*352C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00168 in 340,886 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0030 ( 4 hom., cov: 33)

Exomes 𝑓: 0.00064 ( 1 hom. )

Consequence

NR4A2
NM_006186.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.78

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 2-156325392-G-T is Benign according to our data. Variant chr2-156325392-G-T is described in ClinVar as [Benign]. Clinvar id is 331654.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00297 (452/152158) while in subpopulation AFR AF= 0.00933 (387/41490). AF 95% confidence interval is 0.00856. There are 4 homozygotes in gnomad4. There are 205 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 452 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR4A2	NM_006186.4 linkuse as main transcript	c.*352C>A		3_prime_UTR_variant	8/8	ENST00000339562.9	NP_006177.1	P43354-1F1D8N6Q53EL4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR4A2	ENST00000339562 linkuse as main transcript	c.*352C>A		3_prime_UTR_variant	8/8	1	NM_006186.4	ENSP00000344479.4		P43354-1

Frequencies

GnomAD3 genomes

AF:

0.00297

AC:

451

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00933

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00431

GnomAD4 exome

AF:

0.000636

AC:

120

AN:

188728

Hom.:

Cov.:

AF XY:

0.000574

AC XY:

AN XY:

102770

show subpopulations

Gnomad4 AFR exome

AF:

0.0111

Gnomad4 AMR exome

AF:

0.00145

Gnomad4 ASJ exome

AF:

0.00506

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000840

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000835

Gnomad4 OTH exome

AF:

0.00118

GnomAD4 genome

AF:

0.00297

AC:

452

AN:

152158

Hom.:

Cov.:

AF XY:

0.00276

AC XY:

205

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.00933

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.00375

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00257

Hom.:

Bravo

AF:

0.00344

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Parkinson disease, late-onset

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.80

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