NM_006312.6:c.6001C>G

Variant names:

• chr12-124336867-G-C
• NM_006312.6:c.6001C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006312.6(NCOR2):​c.6001C>G​(p.Pro2001Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P2001S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: NCOR2 NM_006312.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.437

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12615731).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOR2	NM_006312.6	c.6001C>G	p.Pro2001Ala	missense_variant	Exon 40 of 49	ENST00000405201.6	NP_006303.4
NCOR2	NM_001206654.2	c.5971C>G	p.Pro1991Ala	missense_variant	Exon 39 of 48		NP_001193583.1
NCOR2	NM_001077261.4	c.5971C>G	p.Pro1991Ala	missense_variant	Exon 39 of 48		NP_001070729.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOR2	ENST00000405201.6	c.6001C>G	p.Pro2001Ala	missense_variant	Exon 40 of 49	1	NM_006312.6	ENSP00000384018.1
NCOR2	ENST00000429285.6	c.5971C>G	p.Pro1991Ala	missense_variant	Exon 38 of 47	1		ENSP00000400281.2
NCOR2	ENST00000404621.5	c.5971C>G	p.Pro1991Ala	missense_variant	Exon 38 of 47	1		ENSP00000384202.1
NCOR2	ENST00000440187.5	c.*237C>G		downstream_gene_variant		5		ENSP00000396044.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1458894 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725724

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	11
DANN	Benign	0.81
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.74	T;T;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.13	T;T;T;T;T
MetaSVM	Benign	-0.97	T
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.5	D;D;.;D;D
REVEL	Benign	0.078
Sift	Benign	0.030	D;D;.;D;D
Sift4G	Benign	0.61	T;T;D;D;T
Vest4		0.067
MVP		0.32
MPC		0.18
ClinPred		0.092	T
GERP RS		-2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.069
gMVP		0.21

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-124821413;