rs2230944

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

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

Publications

12 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006312.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
NCOR2	NM_006312.6	MANE Select	c.6001C>T	p.Pro2001Ser	missense	Exon 40 of 49	NP_006303.4
NCOR2	NM_001206654.2		c.5971C>T	p.Pro1991Ser	missense	Exon 39 of 48	NP_001193583.1
NCOR2	NM_001077261.4		c.5971C>T	p.Pro1991Ser	missense	Exon 39 of 48	NP_001070729.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
NCOR2	ENST00000405201.6	TSL:1 MANE Select	c.6001C>T	p.Pro2001Ser	missense	Exon 40 of 49	ENSP00000384018.1
NCOR2	ENST00000429285.6	TSL:1	c.5971C>T	p.Pro1991Ser	missense	Exon 38 of 47	ENSP00000400281.2
NCOR2	ENST00000404621.5	TSL:1	c.5971C>T	p.Pro1991Ser	missense	Exon 38 of 47	ENSP00000384202.1

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

GnomAD2 exomes

AF:

0.0466

AC:

11316

AN:

242918

AF XY:

0.0510

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 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

African (AFR)

AF:

0.0525

AC:

1751

AN:

33344

American (AMR)

AF:

0.0273

AC:

1214

AN:

44432

Ashkenazi Jewish (ASJ)

AF:

0.0316

AC:

821

AN:

25974

East Asian (EAS)

AF:

0.0361

AC:

1429

AN:

39622

South Asian (SAS)

AF:

0.124

AC:

10668

AN:

86094

European-Finnish (FIN)

AF:

0.0221

AC:

1160

AN:

52514

Middle Eastern (MID)

AF:

0.0431

AC:

248

AN:

5756

European-Non Finnish (NFE)

AF:

0.0420

AC:

46685

AN:

1110844

Other (OTH)

AF:

0.0462

AC:

2782

AN:

60256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

3856

7713

11569

15426

19282

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1842

3684

5526

7368

9210

<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:

0.0449

AC:

6844

AN:

152272

Hom.:

172

Cov.:

AF XY:

0.0457

AC XY:

3402

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.0521

AC:

2165

AN:

41554

American (AMR)

AF:

0.0376

AC:

575

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0331

AC:

115

AN:

3472

East Asian (EAS)

AF:

0.0284

AC:

147

AN:

5178

South Asian (SAS)

AF:

0.126

AC:

606

AN:

4826

European-Finnish (FIN)

AF:

0.0193

AC:

205

AN:

10620

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0420

AC:

2855

AN:

68000

Other (OTH)

AF:

0.0397

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

323

646

970

1293

1616

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

258

344

430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00669

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

ClinVar submissions as Germline

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

NCOR2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.81

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.77

MetaRNN

Benign

0.0020

MetaSVM

Benign

-0.99

PhyloP100

0.44

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.068

Sift

Benign

0.081

Sift4G

Benign

0.17

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

Mutation Taster

=100/0

polymorphism (auto)

(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

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over