dbSNP rs775842693: NR2F2:p.Gly58Ser (chr15-96332277-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_021005.4(NR2F2):c.172G>A(p.Gly58Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000514 in 1,555,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G58R) has been classified as Uncertain significance.

Frequency

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

Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

NR2F2
NM_021005.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.997

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11116493).

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR2F2	NM_021005.4 link	c.172G>A	p.Gly58Ser	missense_variant	Exon 1 of 3	ENST00000394166.8	NP_066285.1	P24468-1F1D8R0
NR2F2	NM_001145155.2 link	c.44-1799G>A		intron_variant	Intron 1 of 2		NP_001138627.1	P24468-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR2F2	ENST00000394166.8 link	c.172G>A	p.Gly58Ser	missense_variant	Exon 1 of 3	1	NM_021005.4	ENSP00000377721.3		P24468-1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151954

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:

0.0000949

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000639

AC:

AN:

156396

AF XY:

0.0000118

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000163

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000499

AC:

AN:

1403914

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

693404

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31884

American (AMR)

AF:

0.00

AC:

AN:

36550

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25256

East Asian (EAS)

AF:

0.00

AC:

AN:

36178

South Asian (SAS)

AF:

0.00

AC:

AN:

80136

European-Finnish (FIN)

AF:

0.000108

AC:

AN:

46492

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

9.23e-7

AC:

AN:

1083500

Other (OTH)

AF:

0.0000172

AC:

AN:

58216

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151954

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74216

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41416

American (AMR)

AF:

0.00

AC:

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0000949

AC:

AN:

10532

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67982

Other (OTH)

AF:

0.00

AC:

AN:

2090

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:

0.00000378

ExAC

AF:

0.00000871

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.018

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.21

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.41

M_CAP

Pathogenic

0.51

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.59

MutationAssessor

Benign

0.60

PhyloP100

1.0

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

0.42

REVEL

Benign

0.20

Sift

Benign

0.57

Sift4G

Benign

0.72

Polyphen

0.0

Vest4

0.12

MutPred

0.17

Gain of glycosylation at G58 (P = 0.0011);

MVP

0.48

MPC

1.5

ClinPred

0.028

GERP RS

1.4

PromoterAI

-0.0034

Neutral

(source)

Varity_R

0.025

gMVP

0.13

Mutation Taster

=90/10

polymorphism

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over