chr11-63912940-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/21 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

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.069189906).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RCOR2	NM_173587.4	c.899G>A	p.Ser300Asn	missense_variant	Exon 9 of 12	ENST00000301459.5	NP_775858.2
RCOR2	NM_001363648.2	c.899G>A	p.Ser300Asn	missense_variant	Exon 9 of 11		NP_001350577.1
RCOR2	XM_047426828.1	c.1091G>A	p.Ser364Asn	missense_variant	Exon 11 of 14		XP_047282784.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RCOR2	ENST00000301459.5	c.899G>A	p.Ser300Asn	missense_variant	Exon 9 of 12	1	NM_173587.4	ENSP00000301459.4
RCOR2	ENST00000489217.1	n.17G>A		non_coding_transcript_exon_variant	Exon 1 of 3	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 20, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.899G>A (p.S300N) alteration is located in exon 9 (coding exon 9) of the RCOR2 gene. This alteration results from a G to A substitution at nucleotide position 899, causing the serine (S) at amino acid position 300 to be replaced by an asparagine (N). 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	0.12
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
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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-63680412;