Variant 11-63911977-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000301459.5(RCOR2):c.1460C>T(p.Pro487Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000474 in 1,329,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 28)

Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

RCOR2
ENST00000301459.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.02

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25233725).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RCOR2	NM_173587.4 linkuse as main transcript	c.1460C>T	p.Pro487Leu	missense_variant	12/12	ENST00000301459.5	NP_775858.2
RCOR2	XM_047426828.1 linkuse as main transcript	c.1652C>T	p.Pro551Leu	missense_variant	14/14		XP_047282784.1
RCOR2	NM_001363648.2 linkuse as main transcript	c.1230C>T	p.Thr410=	synonymous_variant	11/11		NP_001350577.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
RCOR2	ENST00000301459.5 linkuse as main transcript	c.1460C>T	p.Pro487Leu	missense_variant	12/12	1	NM_173587.4	ENSP00000301459	P1
RCOR2	ENST00000473926.2 linkuse as main transcript	n.254C>T		non_coding_transcript_exon_variant	2/2	3
RCOR2	ENST00000489217.1 linkuse as main transcript	n.703C>T		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes

AF:

0.0000988

AC:

AN:

151806

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000726

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:

0.000177

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000345

AC:

AN:

57998

Hom.:

AF XY:

0.0000334

AC XY:

AN XY:

29906

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000898

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000407

AC:

AN:

1177992

Hom.:

Cov.:

AF XY:

0.0000432

AC XY:

AN XY:

578190

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000329

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000482

Gnomad4 OTH exome

AF:

0.0000199

GnomAD4 genome

AF:

0.0000988

AC:

AN:

151806

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74134

show subpopulations

Gnomad4 AFR

AF:

0.0000726

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000177

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000438

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

The c.1460C>T (p.P487L) alteration is located in exon 12 (coding exon 12) of the RCOR2 gene. This alteration results from a C to T substitution at nucleotide position 1460, causing the proline (P) at amino acid position 487 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.75

BayesDel_addAF

Benign

-0.024

BayesDel_noAF

Benign

-0.27

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

Eigen

Benign

-0.033

Eigen_PC

Benign

0.046

FATHMM_MKL

Uncertain

0.91

LIST_S2

Pathogenic

0.99

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.69

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.15

Sift

Pathogenic

0.0

Sift4G

Benign

0.11

Polyphen

0.39

Vest4

0.39

MutPred

0.23

Loss of glycosylation at P487 (P = 0.0047);

MVP

0.70

MPC

0.93

ClinPred

0.96

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.40

gMVP

0.55

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over