Variant 12-124325482-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006312.6(NCOR2):c.7465G>A(p.Ala2489Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0135 in 1,336,114 control chromosomes in the GnomAD database, including 728 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 91 hom., cov: 30)

Exomes 𝑓: 0.013 ( 637 hom. )

Consequence

NCOR2
NM_006312.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.159

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015721619).

BP6

Variant 12-124325482-C-T is Benign according to our data. Variant chr12-124325482-C-T is described in ClinVar as [Benign]. Clinvar id is 1271601.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOR2	NM_006312.6 link	c.7465G>A	p.Ala2489Thr	missense_variant	49/49	ENST00000405201.6	NP_006303.4	Q9Y618-1
NCOR2	NM_001206654.2 link	c.7435G>A	p.Ala2479Thr	missense_variant	48/48		NP_001193583.1	Q9Y618C9J0Q5
NCOR2	NM_001077261.4 link	c.7297G>A	p.Ala2433Thr	missense_variant	48/48		NP_001070729.2	Q9Y618C9JE98

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOR2	ENST00000405201.6 link	c.7465G>A	p.Ala2489Thr	missense_variant	49/49	1	NM_006312.6	ENSP00000384018.1		Q9Y618-1

Frequencies

GnomAD3 genomes

AF:

0.0178

AC:

2611

AN:

146388

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0117

Gnomad AMI

AF:

0.00224

Gnomad AMR

AF:

0.00566

Gnomad ASJ

AF:

0.0108

Gnomad EAS

AF:

0.0377

Gnomad SAS

AF:

0.118

Gnomad FIN

AF:

0.0968

Gnomad MID

AF:

0.0171

Gnomad NFE

AF:

0.00530

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.0536

AC:

1537

AN:

28692

Hom.:

AF XY:

0.0562

AC XY:

836

AN XY:

14866

show subpopulations

Gnomad AFR exome

AF:

0.0143

Gnomad AMR exome

AF:

0.00504

Gnomad ASJ exome

AF:

0.0117

Gnomad EAS exome

AF:

0.0375

Gnomad SAS exome

AF:

0.176

Gnomad FIN exome

AF:

0.0884

Gnomad NFE exome

AF:

0.00561

Gnomad OTH exome

AF:

0.0381

GnomAD4 exome

AF:

0.0129

AC:

15364

AN:

1189626

Hom.:

637

Cov.:

AF XY:

0.0150

AC XY:

8666

AN XY:

578526

show subpopulations

Gnomad4 AFR exome

AF:

0.0130

Gnomad4 AMR exome

AF:

0.00358

Gnomad4 ASJ exome

AF:

0.0100

Gnomad4 EAS exome

AF:

0.0372

Gnomad4 SAS exome

AF:

0.117

Gnomad4 FIN exome

AF:

0.0817

Gnomad4 NFE exome

AF:

0.00404

Gnomad4 OTH exome

AF:

0.0208

GnomAD4 genome

AF:

0.0179

AC:

2620

AN:

146488

Hom.:

Cov.:

AF XY:

0.0241

AC XY:

1709

AN XY:

71006

show subpopulations

Gnomad4 AFR

AF:

0.0118

Gnomad4 AMR

AF:

0.00565

Gnomad4 ASJ

AF:

0.0108

Gnomad4 EAS

AF:

0.0375

Gnomad4 SAS

AF:

0.119

Gnomad4 FIN

AF:

0.0968

Gnomad4 NFE

AF:

0.00530

Gnomad4 OTH

AF:

0.0138

Alfa

AF:

0.00917

Hom.:

Bravo

AF:

0.00825

ESP6500AA

AF:

0.00729

AC:

ESP6500EA

AF:

0.00350

AC:

ExAC

AF:

0.0135

AC:

1277

Asia WGS

AF:

0.107

AC:

372

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 17, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.92

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.25

LIST_S2

Uncertain

0.92

D;D;D;D;D

MetaRNN

Benign

0.0016

T;T;T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.8

N;N;.;.;N

REVEL

Benign

0.049

Sift

Benign

0.14

T;T;.;.;T

Sift4G

Benign

0.30

T;T;T;T;T

Vest4

0.013

MPC

0.28

ClinPred

0.0098

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.049

gMVP

0.15

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