rs2342924

Positions:

• chr12-124489240-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000405201.6(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 ENST00000405201.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07

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 Benign. Variant got -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/exons	MANE	Protein	UniProt
NCOR2	NM_006312.6	c.106-2672G>A		intron_variant		ENST00000405201.6	NP_006303.4
NCOR2	NM_001077261.4	c.106-2672G>A		intron_variant			NP_001070729.2
NCOR2	NM_001206654.2	c.106-2672G>A		intron_variant			NP_001193583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOR2	ENST00000405201.6	c.106-2672G>A		intron_variant		1	NM_006312.6	ENSP00000384018	P4

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

Gnomad4 AFR AF: 0.916

Gnomad4 AMR AF: 0.824

Gnomad4 ASJ AF: 0.783

Gnomad4 EAS AF: 0.719

Gnomad4 SAS AF: 0.878

Gnomad4 FIN AF: 0.722

Gnomad4 NFE AF: 0.720

Gnomad4 OTH AF: 0.782

Alfa AF: 0.743 Hom.: 42022

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

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: rs2342924; hg19: chr12-124973786;