Genetic Variant NCOR2:p.Asp2512Asn (chr12-124325413-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_006312.6(NCOR2):c.7534G>A(p.Asp2512Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000852 in 657,180 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. D2512Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.000085 ( 0 hom. )

Consequence

NCOR2
NM_006312.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.66

Publications

0 publications found

Variant links:

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]

NCOR2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 56 AD gene.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NCOR2	NM_006312.6	MANE Select	c.7534G>A	p.Asp2512Asn	missense	Exon 49 of 49	NP_006303.4	Q9Y618-1
NCOR2	NM_001206654.2		c.7504G>A	p.Asp2502Asn	missense	Exon 48 of 48	NP_001193583.1	C9J0Q5
NCOR2	NM_001077261.4		c.7366G>A	p.Asp2456Asn	missense	Exon 48 of 48	NP_001070729.2	C9JE98

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NCOR2	ENST00000405201.6	TSL:1 MANE Select	c.7534G>A	p.Asp2512Asn	missense	Exon 49 of 49	ENSP00000384018.1	Q9Y618-1
NCOR2	ENST00000429285.6	TSL:1	c.7504G>A	p.Asp2502Asn	missense	Exon 47 of 47	ENSP00000400281.2	C9J0Q5
NCOR2	ENST00000404621.5	TSL:1	c.7366G>A	p.Asp2456Asn	missense	Exon 47 of 47	ENSP00000384202.1	C9JE98

Frequencies

GnomAD3 genomes

AF:

0.00000716

AC:

AN:

139720

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000233

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000852

AC:

AN:

657180

Hom.:

Cov.:

AF XY:

0.0000788

AC XY:

AN XY:

317088

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

11148

American (AMR)

AF:

0.00

AC:

AN:

3738

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6084

East Asian (EAS)

AF:

0.00

AC:

AN:

7502

South Asian (SAS)

AF:

0.0000340

AC:

AN:

29394

European-Finnish (FIN)

AF:

0.0000468

AC:

AN:

21352

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1414

European-Non Finnish (NFE)

AF:

0.0000958

AC:

AN:

553520

Other (OTH)

AF:

0.0000434

AC:

AN:

23028

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.74

BayesDel_addAF

Benign

-0.010

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.99

M_CAP

Pathogenic

0.35

MetaRNN

Uncertain

0.68

MetaSVM

Benign

-0.35

PhyloP100

7.7

PrimateAI

Pathogenic

0.82

PROVEAN

Pathogenic

-4.7

REVEL

Uncertain

0.35

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.77

MVP

0.63

MPC

0.70

ClinPred

0.99

GERP RS

4.7

Varity_R

0.82

gMVP

0.57

Mutation Taster

=68/32

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over