12-124336867-G-A

Position:

chr12-124336867-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_006312.6(NCOR2):c.6001C>T(p.Pro2001Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0457 in 1,611,108 control chromosomes in the GnomAD database, including 2,192 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.045 ( 172 hom., cov: 33)

Exomes 𝑓: 0.046 ( 2020 hom. )

Consequence

NCOR2
NM_006312.6 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.437

Variant links:

Genes affected

NCOR2 (HGNC:7673): (nuclear receptor corepressor 2) This gene encodes a nuclear receptor co-repressor that mediates transcriptional silencing of certain target genes. The encoded protein is a member of a family of thyroid hormone- and retinoic acid receptor-associated co-repressors. This protein acts as part of a multisubunit complex which includes histone deacetylases to modify chromatin structure that prevents basal transcriptional activity of target genes. Aberrant expression of this gene is associated with certain cancers. Alternate splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Apr 2011]

NCOR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019736588).

BP6

Variant 12-124336867-G-A is Benign according to our data. Variant chr12-124336867-G-A is described in ClinVar as [Benign]. Clinvar id is 3056105.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOR2	NM_006312.6 linkuse as main transcript	c.6001C>T	p.Pro2001Ser	missense_variant	40/49	ENST00000405201.6	NP_006303.4	Q9Y618-1
NCOR2	NM_001206654.2 linkuse as main transcript	c.5971C>T	p.Pro1991Ser	missense_variant	39/48		NP_001193583.1	Q9Y618C9J0Q5
NCOR2	NM_001077261.4 linkuse as main transcript	c.5971C>T	p.Pro1991Ser	missense_variant	39/48		NP_001070729.2	Q9Y618C9JE98

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NCOR2	ENST00000405201.6 linkuse as main transcript	c.6001C>T	p.Pro2001Ser	missense_variant	40/49	1	NM_006312.6	ENSP00000384018.1	Q9Y618-1
NCOR2	ENST00000429285.6 linkuse as main transcript	c.5971C>T	p.Pro1991Ser	missense_variant	38/47	1		ENSP00000400281.2	C9J0Q5
NCOR2	ENST00000404621.5 linkuse as main transcript	c.5971C>T	p.Pro1991Ser	missense_variant	38/47	1		ENSP00000384202.1	C9JE98

Frequencies

GnomAD3 genomes

AF:

0.0449

AC:

6834

AN:

152154

Hom.:

173

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0520

Gnomad AMI

AF:

0.0910

Gnomad AMR

AF:

0.0376

Gnomad ASJ

AF:

0.0331

Gnomad EAS

AF:

0.0285

Gnomad SAS

AF:

0.125

Gnomad FIN

AF:

0.0193

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0420

Gnomad OTH

AF:

0.0401

GnomAD3 exomes

AF:

0.0466

AC:

11316

AN:

242918

Hom.:

400

AF XY:

0.0510

AC XY:

6762

AN XY:

132530

show subpopulations

Gnomad AFR exome

AF:

0.0480

Gnomad AMR exome

AF:

0.0252

Gnomad ASJ exome

AF:

0.0334

Gnomad EAS exome

AF:

0.0222

Gnomad SAS exome

AF:

0.124

Gnomad FIN exome

AF:

0.0213

Gnomad NFE exome

AF:

0.0419

Gnomad OTH exome

AF:

0.0401

GnomAD4 exome

AF:

0.0458

AC:

66758

AN:

1458836

Hom.:

2020

Cov.:

AF XY:

0.0481

AC XY:

34928

AN XY:

725704

show subpopulations

Gnomad4 AFR exome

AF:

0.0525

Gnomad4 AMR exome

AF:

0.0273

Gnomad4 ASJ exome

AF:

0.0316

Gnomad4 EAS exome

AF:

0.0361

Gnomad4 SAS exome

AF:

0.124

Gnomad4 FIN exome

AF:

0.0221

Gnomad4 NFE exome

AF:

0.0420

Gnomad4 OTH exome

AF:

0.0462

GnomAD4 genome

AF:

0.0449

AC:

6844

AN:

152272

Hom.:

172

Cov.:

AF XY:

0.0457

AC XY:

3402

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0521

Gnomad4 AMR

AF:

0.0376

Gnomad4 ASJ

AF:

0.0331

Gnomad4 EAS

AF:

0.0284

Gnomad4 SAS

AF:

0.126

Gnomad4 FIN

AF:

0.0193

Gnomad4 NFE

AF:

0.0420

Gnomad4 OTH

AF:

0.0397

Alfa

AF:

0.00784

Hom.:

Bravo

AF:

0.0438

TwinsUK

AF:

0.0372

AC:

138

ALSPAC

AF:

0.0389

AC:

150

ESP6500AA

AF:

0.0482

AC:

191

ESP6500EA

AF:

0.0343

AC:

284

ExAC

AF:

0.0486

AC:

5847

Asia WGS

AF:

0.0850

AC:

297

AN:

3478

EpiCase

AF:

0.0434

EpiControl

AF:

0.0475

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

NCOR2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 20, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.81

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.77

T;T;T;T;T

MetaRNN

Benign

0.0020

T;T;T;T;T

MetaSVM

Benign

-0.99

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-2.7

D;D;.;D;D

REVEL

Benign

0.068

Sift

Benign

0.081

T;T;.;D;T

Sift4G

Benign

0.17

T;T;T;T;T

Vest4

0.010

MPC

0.21

ClinPred

0.016

GERP RS

-2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.087

gMVP

0.24

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