12-124409638-T-G

Position:

• chr12-124409638-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006312.6(NCOR2):​c.1483-7077A>C variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: NCOR2 NM_006312.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.366

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOR2	NM_006312.6	c.1483-7077A>C		intron_variant		ENST00000405201.6	NP_006303.4
NCOR2	NM_001077261.4	c.1480-7077A>C		intron_variant			NP_001070729.2
NCOR2	NM_001206654.2	c.1480-7077A>C		intron_variant			NP_001193583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOR2	ENST00000405201.6	c.1483-7077A>C		intron_variant		1	NM_006312.6	ENSP00000384018	P4
NCOR2	ENST00000404621.5	c.1480-7077A>C		intron_variant		1		ENSP00000384202	A2
NCOR2	ENST00000429285.6	c.1480-7077A>C		intron_variant		1		ENSP00000400281	A2
NCOR2	ENST00000458234.5	c.1483-7077A>C		intron_variant		1		ENSP00000402808

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.6
DANN	Benign	0.53

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: rs12582168; hg19: chr12-124894184;