dbSNP rs548233693: RCOR2:p.Arg431Pro (chr11-63912145-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_173587.4(RCOR2):c.1292G>C(p.Arg431Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,527,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. 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. R431G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

RCOR2
NM_173587.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.04

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0349679).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RCOR2	NM_173587.4 link	c.1292G>C	p.Arg431Pro	missense_variant	Exon 12 of 12	ENST00000301459.5	NP_775858.2	Q8IZ40
RCOR2	XM_047426828.1 link	c.1484G>C	p.Arg495Pro	missense_variant	Exon 14 of 14		XP_047282784.1
RCOR2	NM_001363648.2 link	c.1062G>C	p.Pro354Pro	synonymous_variant	Exon 11 of 11		NP_001350577.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RCOR2	ENST00000301459.5 link	c.1292G>C	p.Arg431Pro	missense_variant	Exon 12 of 12	1	NM_173587.4	ENSP00000301459.4	Q8IZ40
RCOR2	ENST00000473926.2 link	n.86G>C		non_coding_transcript_exon_variant	Exon 2 of 2	3
RCOR2	ENST00000489217.1 link	n.535G>C		non_coding_transcript_exon_variant	Exon 3 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.0000265

AC:

AN:

151122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000626

AC:

AN:

127892

Hom.:

AF XY:

0.0000145

AC XY:

AN XY:

69198

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000941

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000197

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000240

AC:

AN:

1376422

Hom.:

Cov.:

AF XY:

0.0000221

AC XY:

AN XY:

679486

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000614

Gnomad4 EAS exome

AF:

0.0000558

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000112

Gnomad4 OTH exome

AF:

0.0000698

GnomAD4 genome

AF:

0.0000265

AC:

AN:

151122

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73752

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000855

Hom.:

ExAC

AF:

0.0000380

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.70

DEOGEN2

Benign

0.012

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.67

M_CAP

Benign

0.0093

MetaRNN

Benign

0.035

MetaSVM

Benign

-1.1

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-0.010

REVEL

Benign

0.066

Sift

Benign

0.29

Sift4G

Benign

0.38

Polyphen

0.0060

Vest4

0.11

MVP

0.42

MPC

1.3

ClinPred

0.33

GERP RS

4.7

Varity_R

0.19

gMVP

0.42

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over