11-63915252-G-A

Position:

• chr11-63915252-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000301459.5(RCOR2):​c.191C>T​(p.Pro64Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RCOR2 ENST00000301459.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.11

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29206926).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RCOR2	NM_173587.4	c.191C>T	p.Pro64Leu	missense_variant	3/12	ENST00000301459.5	NP_775858.2
RCOR2	NM_001363648.2	c.191C>T	p.Pro64Leu	missense_variant	3/11		NP_001350577.1
RCOR2	XM_047426828.1	c.383C>T	p.Pro128Leu	missense_variant	5/14		XP_047282784.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RCOR2	ENST00000301459.5	c.191C>T	p.Pro64Leu	missense_variant	3/12	1	NM_173587.4	ENSP00000301459	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 13, 2023

The c.191C>T (p.P64L) alteration is located in exon 3 (coding exon 3) of the RCOR2 gene. This alteration results from a C to T substitution at nucleotide position 191, causing the proline (P) at amino acid position 64 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	Benign	0.24
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Benign	0.95
DEOGEN2	Benign	0.050	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.54	N
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.17
Sift	Benign	0.26	T
Sift4G	Benign	0.32	T
Polyphen		0.91	P
Vest4		0.28
MutPred		0.49		Loss of disorder (P = 0.0391);
MVP		0.58
MPC		1.0
ClinPred		0.79	D
GERP RS		4.7
Varity_R		0.13
gMVP		0.67

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

Other links and lift over

dbSNP: rs1941839518; hg19: chr11-63682724;