chr12-124372487-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_006312.6(NCOR2):c.2342G>A(p.Gly781Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,574,702 control chromosomes in the GnomAD database, including 15,190 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.12 ( 1230 hom., cov: 27)

Exomes 𝑓: 0.14 ( 13960 hom. )

Consequence

NCOR2
NM_006312.6 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.679

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=0.0014986098).

BP6

Variant 12-124372487-C-T is Benign according to our data. Variant chr12-124372487-C-T is described in ClinVar as [Benign]. Clinvar id is 3058956.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOR2	NM_006312.6 link	c.2342G>A	p.Gly781Glu	missense_variant	Exon 22 of 49	ENST00000405201.6	NP_006303.4	Q9Y618-1
NCOR2	NM_001206654.2 link	c.2288G>A	p.Gly763Glu	missense_variant	Exon 21 of 48		NP_001193583.1	Q9Y618C9J0Q5
NCOR2	NM_001077261.4 link	c.2288G>A	p.Gly763Glu	missense_variant	Exon 21 of 48		NP_001070729.2	Q9Y618C9JE98

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOR2	ENST00000405201.6 link	c.2342G>A	p.Gly781Glu	missense_variant	Exon 22 of 49	1	NM_006312.6	ENSP00000384018.1		Q9Y618-1

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17371

AN:

149774

Hom.:

1226

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0836

Gnomad AMI

AF:

0.153

Gnomad AMR

AF:

0.129

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.000581

Gnomad SAS

AF:

0.0702

Gnomad FIN

AF:

0.130

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.141

Gnomad OTH

AF:

0.119

GnomAD2 exomes

AF:

0.118

AC:

24785

AN:

210060

AF XY:

0.117

show subpopulations

Gnomad AFR exome

AF:

0.0869

Gnomad AMR exome

AF:

0.135

Gnomad ASJ exome

AF:

0.142

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.151

Gnomad NFE exome

AF:

0.141

Gnomad OTH exome

AF:

0.133

GnomAD4 exome

AF:

0.135

AC:

192640

AN:

1424812

Hom.:

13960

Cov.:

AF XY:

0.134

AC XY:

94879

AN XY:

708336

show subpopulations

Gnomad4 AFR exome

AF:

0.0802

AC:

2613

AN:

32582

Gnomad4 AMR exome

AF:

0.135

AC:

5562

AN:

41306

Gnomad4 ASJ exome

AF:

0.143

AC:

3499

AN:

24518

Gnomad4 EAS exome

AF:

0.000152

AC:

AN:

39500

Gnomad4 SAS exome

AF:

0.0875

AC:

7309

AN:

83498

Gnomad4 FIN exome

AF:

0.161

AC:

5969

AN:

37172

Gnomad4 NFE exome

AF:

0.145

AC:

159439

AN:

1101838

Gnomad4 Remaining exome

AF:

0.131

AC:

7758

AN:

59230

Heterozygous variant carriers

7740

15481

23221

30962

38702

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

5632

11264

16896

22528

28160

<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:

0.116

AC:

17385

AN:

149890

Hom.:

1230

Cov.:

AF XY:

0.114

AC XY:

8314

AN XY:

73142

show subpopulations

Gnomad4 AFR

AF:

0.0837

AC:

0.0837012

AN:

0.0837012

Gnomad4 AMR

AF:

0.129

AC:

0.128921

AN:

0.128921

Gnomad4 ASJ

AF:

0.132

AC:

0.132327

AN:

0.132327

Gnomad4 EAS

AF:

0.000583

AC:

0.000582751

AN:

0.000582751

Gnomad4 SAS

AF:

0.0700

AC:

0.070034

AN:

0.070034

Gnomad4 FIN

AF:

0.130

AC:

0.130093

AN:

0.130093

Gnomad4 NFE

AF:

0.141

AC:

0.141273

AN:

0.141273

Gnomad4 OTH

AF:

0.118

AC:

0.118015

AN:

0.118015

Heterozygous variant carriers

642

1284

1925

2567

3209

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

190

380

570

760

950

<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:

0.0951

Hom.:

216

Bravo

AF:

0.116

TwinsUK

AF:

0.147

AC:

545

ALSPAC

AF:

0.148

AC:

569

ESP6500AA

AF:

0.0734

AC:

277

ESP6500EA

AF:

0.140

AC:

1147

ExAC

AF:

0.120

AC:

14201

Asia WGS

AF:

0.0330

AC:

114

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

NCOR2-related disorder

Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

0.051

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.55

CADD

Benign

2.2

DANN

Benign

0.45

DEOGEN2

Benign

0.26

T;.;.;.;.;T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0059

LIST_S2

Benign

0.26

T;T;T;T;T;T;T

MetaRNN

Benign

0.0015

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.1

N;.;.;.;.;.;.

PrimateAI

Benign

0.41

PROVEAN

Benign

1.4

N;N;.;.;N;N;N

REVEL

Benign

0.032

Sift

Benign

0.93

T;T;.;.;T;T;D

Sift4G

Benign

0.16

T;T;T;T;T;.;.

Polyphen

0.0

.;.;.;.;B;.;.

Vest4

0.029

MPC

0.22

ClinPred

0.0016

GERP RS

-0.62

Varity_R

0.042

gMVP

0.15

Mutation Taster

=100/0

polymorphism (auto)

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