Genetic Variant RCOR2:p.Arg498His (chr11-63911944-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173587.4(RCOR2):c.1493G>A(p.Arg498His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000271 in 663,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R498C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 21)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

RCOR2
NM_173587.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.29

Publications

1 publications found

Variant links:

Genes affected

RCOR2 (HGNC:27455): (REST corepressor 2) Predicted to enable transcription corepressor activity. Predicted to be involved in histone deacetylation; negative regulation of transcription, DNA-templated; and regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of histone deacetylase complex and transcription regulator complex. [provided by Alliance of Genome Resources, Apr 2022]

RCOR2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09935883).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173587.4. 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
	RCOR2	NM_173587.4	MANE Select	c.1493G>A	p.Arg498His	missense	Exon 12 of 12	NP_775858.2	Q8IZ40
	RCOR2	NM_001363648.2		c.1263G>A	p.Pro421Pro	synonymous	Exon 11 of 11	NP_001350577.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RCOR2	ENST00000301459.5	TSL:1 MANE Select	c.1493G>A	p.Arg498His	missense	Exon 12 of 12	ENSP00000301459.4	Q8IZ40
RCOR2	ENST00000864867.1		c.1496G>A	p.Arg499His	missense	Exon 13 of 13	ENSP00000534926.1
RCOR2	ENST00000917267.1		c.1493G>A	p.Arg498His	missense	Exon 13 of 13	ENSP00000587326.1

Frequencies

GnomAD3 genomes

AF:

0.0000262

AC:

AN:

76454

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000563

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000456

AC:

AN:

43866

AF XY:

0.0000435

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000548

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000273

AC:

AN:

586562

Hom.:

Cov.:

AF XY:

0.0000381

AC XY:

AN XY:

288626

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

12130

American (AMR)

AF:

0.00

AC:

AN:

9256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7728

East Asian (EAS)

AF:

0.00

AC:

AN:

10674

South Asian (SAS)

AF:

0.0000487

AC:

AN:

41046

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10026

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1504

European-Non Finnish (NFE)

AF:

0.0000297

AC:

AN:

471350

Other (OTH)

AF:

0.00

AC:

AN:

22848

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

AF:

0.0000262

AC:

AN:

76454

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

37018

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20022

American (AMR)

AF:

0.00

AC:

AN:

8204

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1976

East Asian (EAS)

AF:

0.00

AC:

AN:

2808

South Asian (SAS)

AF:

0.00

AC:

AN:

2022

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4080

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.0000563

AC:

AN:

35548

Other (OTH)

AF:

0.00

AC:

AN:

1118

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.030

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.084

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.74

M_CAP

Benign

0.011

MetaRNN

Benign

0.099

MetaSVM

Benign

-1.1

PhyloP100

1.3

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.2

REVEL

Benign

0.068

Sift

Uncertain

0.020

Sift4G

Benign

0.21

Polyphen

0.035

Vest4

0.074

MutPred

0.17

Loss of methylation at R498 (P = 0.0151)

MVP

0.43

MPC

1.1

ClinPred

0.18

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.21

Mutation Taster

=92/8

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over