Variant 19-17235654-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_005234.4(NR2F6):c.785C>T(p.Ala262Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 1,519,978 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000051 ( 0 hom. )

Consequence

NR2F6
NM_005234.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.53

Variant links:

Genes affected

NR2F6 (HGNC:7977): (nuclear receptor subfamily 2 group F member 6) Enables DNA-binding transcription factor activity and sequence-specific double-stranded DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

NR2F6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR2F6	NM_005234.4 linkuse as main transcript	c.785C>T	p.Ala262Val	missense_variant	3/4	ENST00000291442.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR2F6	ENST00000291442.4 linkuse as main transcript	c.785C>T	p.Ala262Val	missense_variant	3/4	1	NM_005234.4	P1
NR2F6	ENST00000596878.1 linkuse as main transcript			downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152150

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:

0.000578

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000794

AC:

AN:

113296

Hom.:

AF XY:

0.0000632

AC XY:

AN XY:

63324

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00108

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000512

AC:

AN:

1367828

Hom.:

Cov.:

AF XY:

0.00000592

AC XY:

AN XY:

675164

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000206

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000466

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 27, 2023

The c.785C>T (p.A262V) alteration is located in exon 3 (coding exon 3) of the NR2F6 gene. This alteration results from a C to T substitution at nucleotide position 785, causing the alanine (A) at amino acid position 262 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Benign

-0.091

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.78

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Benign

0.42

LIST_S2

Pathogenic

0.99

M_CAP

Pathogenic

0.86

MetaRNN

Uncertain

0.71

MetaSVM

Pathogenic

1.0

MutationAssessor

Benign

1.8

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.93

PROVEAN

Uncertain

-3.2

REVEL

Pathogenic

0.84

Sift

Benign

0.067

Sift4G

Benign

0.13

Polyphen

0.99

Vest4

0.42

MutPred

0.71

Gain of sheet (P = 0.1208);

MVP

0.97

MPC

1.8

ClinPred

0.26

GERP RS

4.7

Varity_R

0.40

gMVP

0.52

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