dbSNP rs1555446980: NR2F2:p.Gln22* (chr15-96332169-C-T) – ACMG Classification: Pathogenic (12 pts)

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_021005.4(NR2F2):c.64C>T(p.Gln22*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NR2F2
NM_021005.4 stop_gained

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 5.36

Publications

0 publications found

Variant links:

Genes affected

NR2F2 (HGNC:7976): (nuclear receptor subfamily 2 group F member 2) This gene encodes a member of the steroid thyroid hormone superfamily of nuclear receptors. The encoded protein is a ligand inducible transcription factor that is involved in the regulation of many different genes. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

NR2F2 links:

NR2F2-AS1 (HGNC:44222): (NR2F2 antisense RNA 1)

NR2F2-AS1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_021005.4, 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: Pathogenic. The variant received 12 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 31 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 15-96332169-C-T is Pathogenic according to our data. Variant chr15-96332169-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 521441.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021005.4. 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
	NR2F2	NM_021005.4	MANE Select	c.64C>T	p.Gln22*	stop_gained	Exon 1 of 3	NP_066285.1	F1D8R0
	NR2F2	NM_001145155.2		c.44-1907C>T		intron	N/A	NP_001138627.1	P24468-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NR2F2	ENST00000394166.8	TSL:1 MANE Select	c.64C>T	p.Gln22*	stop_gained	Exon 1 of 3	ENSP00000377721.3	P24468-1
NR2F2	ENST00000421109.6	TSL:1	c.44-1907C>T		intron	N/A	ENSP00000401674.2	P24468-2
NR2F2	ENST00000961130.1		c.64C>T	p.Gln22*	stop_gained	Exon 2 of 4	ENSP00000631189.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1186342

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

578318

African (AFR)

AF:

0.00

AC:

AN:

23574

American (AMR)

AF:

0.00

AC:

AN:

11318

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16306

East Asian (EAS)

AF:

0.00

AC:

AN:

26312

South Asian (SAS)

AF:

0.00

AC:

AN:

43430

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35948

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

978512

Other (OTH)

AF:

0.00

AC:

AN:

47630

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Pathogenic

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.62

BayesDel_noAF

Pathogenic

0.58

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Pathogenic

0.98

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

0.97

PhyloP100

5.4

PromoterAI

0.039

Neutral

(source)

Mutation Taster

=2/198

disease causing (ClinVar)

(source)

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

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over