12-124326365-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006312.6(NCOR2):c.7189G>A(p.Gly2397Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000187 in 1,489,654 control chromosomes in the GnomAD database, including 1 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00096 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000099 ( 0 hom. )

Consequence

NCOR2
NM_006312.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.18

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009930432).

BP6

Variant 12-124326365-C-T is Benign according to our data. Variant chr12-124326365-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3044033.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 146 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NCOR2	NM_006312.6 linkuse as main transcript	c.7189G>A	p.Gly2397Ser	missense_variant	48/49	ENST00000405201.6
NCOR2	NM_001206654.2 linkuse as main transcript	c.7159G>A	p.Gly2387Ser	missense_variant	47/48
NCOR2	NM_001077261.4 linkuse as main transcript	c.7021G>A	p.Gly2341Ser	missense_variant	47/48

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCOR2	ENST00000405201.6 linkuse as main transcript	c.7189G>A	p.Gly2397Ser	missense_variant	48/49	1	NM_006312.6	P4	Q9Y618-1

Frequencies

GnomAD3 genomes

AF:

0.000959

AC:

146

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00333

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000356

AC:

AN:

140458

Hom.:

AF XY:

0.000220

AC XY:

AN XY:

77306

show subpopulations

Gnomad AFR exome

AF:

0.00446

Gnomad AMR exome

AF:

0.000156

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000142

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000995

AC:

133

AN:

1337340

Hom.:

Cov.:

AF XY:

0.0000838

AC XY:

AN XY:

656514

show subpopulations

Gnomad4 AFR exome

AF:

0.00338

Gnomad4 AMR exome

AF:

0.000173

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000292

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000151

Gnomad4 OTH exome

AF:

0.000272

GnomAD4 genome

AF:

0.000959

AC:

146

AN:

152314

Hom.:

Cov.:

AF XY:

0.000792

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00332

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000178

Hom.:

Bravo

AF:

0.00111

ESP6500AA

AF:

0.00277

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000360

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

NCOR2-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 10, 2022

This variant is classified as likely 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

-0.45

BayesDel_noAF

Benign

-0.42

Cadd

Benign

Dann

Benign

0.96

Eigen

Benign

-0.035

Eigen_PC

Benign

-0.076

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.87

D;D;D;D;D

M_CAP

Benign

0.019

MetaRNN

Benign

0.0099

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.98

D;D;D;D;D;D

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-3.4

D;D;.;.;D

REVEL

Benign

0.11

Sift

Benign

0.17

T;T;.;.;T

Sift4G

Benign

0.099

T;T;T;T;T

Vest4

0.25

MVP

0.55

MPC

0.62

ClinPred

0.056

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.069

gMVP

0.14

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