11-63912146-G-C

Variant summary

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

The NM_173587.4(RCOR2):ā€‹c.1291C>Gā€‹(p.Arg431Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000392 in 1,530,152 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. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 31)
Exomes š‘“: 0.0000029 ( 0 hom. )

Consequence

RCOR2
NM_173587.4 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.38
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]

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=0.17161185).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RCOR2NM_173587.4 linkuse as main transcriptc.1291C>G p.Arg431Gly missense_variant 12/12 ENST00000301459.5 NP_775858.2 Q8IZ40
RCOR2NM_001363648.2 linkuse as main transcriptc.1061C>G p.Pro354Arg missense_variant 11/11 NP_001350577.1
RCOR2XM_047426828.1 linkuse as main transcriptc.1483C>G p.Arg495Gly missense_variant 14/14 XP_047282784.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RCOR2ENST00000301459.5 linkuse as main transcriptc.1291C>G p.Arg431Gly missense_variant 12/121 NM_173587.4 ENSP00000301459.4 Q8IZ40
RCOR2ENST00000473926.2 linkuse as main transcriptn.85C>G non_coding_transcript_exon_variant 2/23
RCOR2ENST00000489217.1 linkuse as main transcriptn.534C>G non_coding_transcript_exon_variant 3/33

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
151900
Hom.:
0
Cov.:
31
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000290
AC:
4
AN:
1378252
Hom.:
0
Cov.:
33
AF XY:
0.00000294
AC XY:
2
AN XY:
680448
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000372
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
151900
Hom.:
0
Cov.:
31
AF XY:
0.0000270
AC XY:
2
AN XY:
74188
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.00000378

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 submitterclinical testingAmbry GeneticsDec 19, 2022The c.1291C>G (p.R431G) alteration is located in exon 12 (coding exon 12) of the RCOR2 gene. This alteration results from a C to G substitution at nucleotide position 1291, causing the arginine (R) at amino acid position 431 to be replaced by a glycine (G). 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
Benign
0.081
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
18
DANN
Benign
0.90
DEOGEN2
Benign
0.018
T
Eigen
Benign
-0.44
Eigen_PC
Benign
-0.39
FATHMM_MKL
Benign
0.70
D
LIST_S2
Benign
0.71
T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.17
T
MetaSVM
Benign
-1.1
T
PrimateAI
Uncertain
0.77
T
PROVEAN
Benign
-0.49
N
REVEL
Benign
0.060
Sift
Benign
0.11
T
Sift4G
Benign
0.24
T
Polyphen
0.65
P
Vest4
0.22
MutPred
0.14
Gain of relative solvent accessibility (P = 0.0166);
MVP
0.45
MPC
1.1
ClinPred
0.38
T
GERP RS
2.8
Varity_R
0.098
gMVP
0.39

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs1179884901; hg19: chr11-63679618; API