12-124326258-C-A

Variant names:

• chr12-124326258-C-A
• rs187350105
• NM_006312.6:c.7296G>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_006312.6(NCOR2):​c.7296G>T​(p.Ser2432Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000213 in 1,407,322 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S2432S) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: NCOR2 NM_006312.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.77
• 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.03).
• BP7: Synonymous conserved (PhyloP=-3.77 with no splicing effect.

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.7296G>T	p.Ser2432Ser	synonymous	Exon 48 of 49	NP_006303.4	Q9Y618-1
	NCOR2	NM_001206654.2		c.7266G>T	p.Ser2422Ser	synonymous	Exon 47 of 48	NP_001193583.1	C9J0Q5
	NCOR2	NM_001077261.4		c.7128G>T	p.Ser2376Ser	synonymous	Exon 47 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.7296G>T	p.Ser2432Ser	synonymous	Exon 48 of 49	ENSP00000384018.1	Q9Y618-1
	NCOR2	ENST00000429285.6	TSL:1	c.7266G>T	p.Ser2422Ser	synonymous	Exon 46 of 47	ENSP00000400281.2	C9J0Q5
	NCOR2	ENST00000404621.5	TSL:1	c.7128G>T	p.Ser2376Ser	synonymous	Exon 46 of 47	ENSP00000384202.1	C9JE98

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000213 AC: 3 AN: 1407322 Hom.: 0 Cov.: 31 AF XY: 0.00000144 AC XY: 1 AN XY: 696430

African (AFR) AF: 0.00 AC: 0 AN: 31722

American (AMR) AF: 0.00 AC: 0 AN: 36806

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24764

East Asian (EAS) AF: 0.00 AC: 0 AN: 36532

South Asian (SAS) AF: 0.00 AC: 0 AN: 80434

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46940

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5618

European-Non Finnish (NFE) AF: 0.00000276 AC: 3 AN: 1086130

Other (OTH) AF: 0.00 AC: 0 AN: 58376

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	3.7
DANN	Benign	0.85
PhyloP100		-3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	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: rs187350105; hg19: chr12-124810804;