NM_006312.6:c.7448C>A

Variant names:

• chr12-124325499-G-T
• rs1488001578
• NM_006312.6:c.7448C>A

Variant summary

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

The NM_006312.6(NCOR2):​c.7448C>A​(p.Ala2483Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NCOR2 NM_006312.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21

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=0.10951516).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOR2	NM_006312.6	c.7448C>A	p.Ala2483Glu	missense_variant	Exon 49 of 49	ENST00000405201.6	NP_006303.4
NCOR2	NM_001206654.2	c.7418C>A	p.Ala2473Glu	missense_variant	Exon 48 of 48		NP_001193583.1
NCOR2	NM_001077261.4	c.7280C>A	p.Ala2427Glu	missense_variant	Exon 48 of 48		NP_001070729.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOR2	ENST00000405201.6	c.7448C>A	p.Ala2483Glu	missense_variant	Exon 49 of 49	1	NM_006312.6	ENSP00000384018.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1 AN: 151364 Hom.: 0 Cov.: 30 FAILED QC

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1206518 Hom.: 0 Cov.: 38 AF XY: 0.00 AC XY: 0 AN XY: 586356

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

Bravo AF: 0.00000378

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Benign	0.61
Eigen	Benign	-0.93
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.80	T;T;T;T;T
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.11	T;T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-2.3	N;N;D;.;N
REVEL	Benign	0.061
Sift	Uncertain	0.0040	D;D;D;.;D
Sift4G	Uncertain	0.056	T;T;D;D;T
Vest4		0.15
MVP		0.22
MPC		0.41
ClinPred		0.19	T
GERP RS		-0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
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

Other links and lift over

dbSNP: rs1488001578; hg19: chr12-124810045;