NM_006312.6:c.7483T>C

Variant names:

• chr12-124325464-A-G
• rs985828412
• NM_006312.6:c.7483T>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3 BS2

The NM_006312.6(NCOR2):​c.7483T>C​(p.Trp2495Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000178 in 1,294,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: NCOR2 NM_006312.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.08
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.772
• BS2: High AC in GnomAdExome4 at 21 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOR2	NM_006312.6	MANE Select	c.7483T>C	p.Trp2495Arg	missense	Exon 49 of 49	NP_006303.4	Q9Y618-1
	NCOR2	NM_001206654.2		c.7453T>C	p.Trp2485Arg	missense	Exon 48 of 48	NP_001193583.1	C9J0Q5
	NCOR2	NM_001077261.4		c.7315T>C	p.Trp2439Arg	missense	Exon 48 of 48	NP_001070729.2	C9JE98

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOR2	ENST00000405201.6	TSL:1 MANE Select	c.7483T>C	p.Trp2495Arg	missense	Exon 49 of 49	ENSP00000384018.1	Q9Y618-1
	NCOR2	ENST00000429285.6	TSL:1	c.7453T>C	p.Trp2485Arg	missense	Exon 47 of 47	ENSP00000400281.2	C9J0Q5
	NCOR2	ENST00000404621.5	TSL:1	c.7315T>C	p.Trp2439Arg	missense	Exon 47 of 47	ENSP00000384202.1	C9JE98

Frequencies

GnomAD3 genomes AF: 0.0000143 AC: 2 AN: 140022 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000439

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 37268 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000182 AC: 21 AN: 1154572 Hom.: 0 Cov.: 38 AF XY: 0.0000142 AC XY: 8 AN XY: 562060

African (AFR) AF: 0.00 AC: 0 AN: 22184

American (AMR) AF: 0.00 AC: 0 AN: 11340

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15296

East Asian (EAS) AF: 0.000784 AC: 18 AN: 22970

South Asian (SAS) AF: 0.0000199 AC: 1 AN: 50126

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37662

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3156

European-Non Finnish (NFE) AF: 0.00000106 AC: 1 AN: 947278

Other (OTH) AF: 0.0000224 AC: 1 AN: 44560

GnomAD4 genome AF: 0.0000143 AC: 2 AN: 140022 Hom.: 0 Cov.: 30 AF XY: 0.0000296 AC XY: 2 AN XY: 67558

African (AFR) AF: 0.00 AC: 0 AN: 36730

American (AMR) AF: 0.00 AC: 0 AN: 12814

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3408

East Asian (EAS) AF: 0.000439 AC: 2 AN: 4552

South Asian (SAS) AF: 0.00 AC: 0 AN: 4390

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 268

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66162

Other (OTH) AF: 0.00 AC: 0 AN: 1926

Alfa AF: 0.00 Hom.: 0

Asia WGS AF: 0.000289 AC: 1 AN: 3476

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	26
DANN	Uncertain	0.97
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.76	T
M_CAP	Uncertain	0.23	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-1.0	T
PhyloP100		6.1
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-10	D
REVEL	Uncertain	0.31
Sift	Benign	0.084	T
Sift4G	Uncertain	0.053	T
Vest4		0.76
MVP		0.57
MPC		0.88
ClinPred		1.0	D
GERP RS		4.7
Varity_R		0.65
gMVP		0.38
Mutation Taster		=74/26	polymorphism

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

Other links and lift over

dbSNP: rs985828412; hg19: chr12-124810010;