Genetic Variant NR2F2:p.Pro16Pro (chr15-96332153-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6BP7

The NM_021005.4(NR2F2):c.48C>T(p.Pro16Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000295 in 1,354,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000025 ( 0 hom. )

Consequence

NR2F2
NM_021005.4 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.978

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 15-96332153-C-T is Benign according to our data. Variant chr15-96332153-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3051780.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.978 with no splicing effect.

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.48C>T	p.Pro16Pro	synonymous	Exon 1 of 3	NP_066285.1	F1D8R0
	NR2F2	NM_001145155.2		c.44-1923C>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.48C>T	p.Pro16Pro	synonymous	Exon 1 of 3	ENSP00000377721.3	P24468-1
NR2F2	ENST00000421109.6	TSL:1	c.44-1923C>T		intron	N/A	ENSP00000401674.2	P24468-2
NR2F2	ENST00000961130.1		c.48C>T	p.Pro16Pro	synonymous	Exon 2 of 4	ENSP00000631189.1

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151674

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000249

AC:

AN:

1203004

Hom.:

Cov.:

AF XY:

0.00000511

AC XY:

AN XY:

587414

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23888

American (AMR)

AF:

0.00

AC:

AN:

12826

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17208

East Asian (EAS)

AF:

0.00

AC:

AN:

26522

South Asian (SAS)

AF:

0.0000214

AC:

AN:

46798

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38108

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3438

European-Non Finnish (NFE)

AF:

0.00000203

AC:

AN:

985868

Other (OTH)

AF:

0.00

AC:

AN:

48348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151782

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74196

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41478

American (AMR)

AF:

0.00

AC:

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5124

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10450

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67872

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

NR2F2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.96

PhyloP100

0.98

PromoterAI

0.0054

Neutral

(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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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