chr11-63912940-C-T

Variant names:

• chr11-63912940-C-T
• rs1476311673
• NM_173587.4:c.899G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173587.4(RCOR2):​c.899G>A​(p.Ser300Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: RCOR2 NM_173587.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.477
• Publications: 0 publications found

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

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=0.069189906).

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.899G>A	p.Ser300Asn	missense	Exon 9 of 12	NP_775858.2	Q8IZ40
	RCOR2	NM_001363648.2		c.899G>A	p.Ser300Asn	missense	Exon 9 of 11	NP_001350577.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCOR2	ENST00000301459.5	TSL:1 MANE Select	c.899G>A	p.Ser300Asn	missense	Exon 9 of 12	ENSP00000301459.4	Q8IZ40
	RCOR2	ENST00000864867.1		c.902G>A	p.Ser301Asn	missense	Exon 10 of 13	ENSP00000534926.1
	RCOR2	ENST00000917267.1		c.899G>A	p.Ser300Asn	missense	Exon 10 of 13	ENSP00000587326.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	20
DANN	Benign	0.91
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.40	N
PhyloP100		0.48
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	0.74	N
REVEL	Benign	0.092
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0030	B
Vest4		0.15
MutPred		0.22		Gain of helix (P = 0.0496)
MVP		0.35
MPC		0.13
ClinPred		0.44	T
GERP RS		4.6
Varity_R		0.084
gMVP		0.58
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs1476311673; hg19: chr11-63680412;