12-124489240-C-T

Variant names:

• chr12-124489240-C-T
• rs2342924
• NM_006312.6:c.106-2672G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006312.6(NCOR2):​c.106-2672G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.791 in 152,040 control chromosomes in the GnomAD database, including 48,091 homozygotes. 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: 𝑓 0.79 (48091 hom., cov: 31)
• Consequence: NCOR2 NM_006312.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOR2	NM_006312.6	c.106-2672G>A		intron_variant	Intron 3 of 48	ENST00000405201.6	NP_006303.4
NCOR2	NM_001206654.2	c.106-2672G>A		intron_variant	Intron 3 of 47		NP_001193583.1
NCOR2	NM_001077261.4	c.106-2672G>A		intron_variant	Intron 3 of 47		NP_001070729.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOR2	ENST00000405201.6	c.106-2672G>A		intron_variant	Intron 3 of 48	1	NM_006312.6	ENSP00000384018.1

Frequencies

GnomAD3 genomes AF: 0.791 AC: 120112 AN: 151922 Hom.: 48028 Cov.: 31

Gnomad AFR AF: 0.916

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.823

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.878

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.781

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

GnomAD4 genome AF: 0.791 AC: 120233 AN: 152040 Hom.: 48091 Cov.: 31 AF XY: 0.792 AC XY: 58883 AN XY: 74306

African (AFR) AF: 0.916 AC: 38000 AN: 41492

American (AMR) AF: 0.824 AC: 12576 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.783 AC: 2720 AN: 3472

East Asian (EAS) AF: 0.719 AC: 3721 AN: 5172

South Asian (SAS) AF: 0.878 AC: 4230 AN: 4818

European-Finnish (FIN) AF: 0.722 AC: 7620 AN: 10554

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.720 AC: 48908 AN: 67950

Other (OTH) AF: 0.782 AC: 1651 AN: 2110

Alfa AF: 0.752 Hom.: 56046

Bravo AF: 0.802

Asia WGS AF: 0.834 AC: 2900 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.14
DANN	Benign	0.60
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs2342924; hg19: chr12-124973786;