chr12-124341916-C-G

Variant names:

• chr12-124341916-C-G
• rs2229840
• NM_006312.6:c.5095G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006312.6(NCOR2):​c.5095G>C​(p.Ala1699Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1699T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NCOR2 NM_006312.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.72
• Publications: 51 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.5095G>C	p.Ala1699Pro	missense	Exon 36 of 49	NP_006303.4	Q9Y618-1
	NCOR2	NM_001206654.2		c.5065G>C	p.Ala1689Pro	missense	Exon 35 of 48	NP_001193583.1	C9J0Q5
	NCOR2	NM_001077261.4		c.5065G>C	p.Ala1689Pro	missense	Exon 35 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.5095G>C	p.Ala1699Pro	missense	Exon 36 of 49	ENSP00000384018.1	Q9Y618-1
	NCOR2	ENST00000429285.6	TSL:1	c.5065G>C	p.Ala1689Pro	missense	Exon 34 of 47	ENSP00000400281.2	C9J0Q5
	NCOR2	ENST00000404621.5	TSL:1	c.5065G>C	p.Ala1689Pro	missense	Exon 34 of 47	ENSP00000384202.1	C9JE98

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 7641

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Uncertain	0.99
Eigen	Benign	0.17
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.057	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.70	T
PhyloP100		4.7
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.22
Sift	Benign	0.040	D
Sift4G	Benign	0.11	T
Polyphen		1.0	D
Vest4		0.64
MutPred		0.42		Gain of loop (P = 3e-04)
MVP		0.46
MPC		0.81
ClinPred		0.94	D
GERP RS		4.4
PromoterAI		-0.0016	Neutral
Varity_R		0.73
gMVP		0.69
Mutation Taster		=65/35	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: rs2229840; hg19: chr12-124826462;