chr22-17549440-C-G

Variant names:

• chr22-17549440-C-G
• NM_001290047.2:c.4153C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM2 PP5_Moderate BP4

The NM_001290047.2(CECR2):​c.4153C>G​(p.Gln1385Glu) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CECR2 NM_001290047.2 missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 2.64
• Publications: 0 publications found

Genes affected

CECR2 (HGNC:1840): (CECR2 histone acetyl-lysine reader) This gene encodes a bromodomain-containing protein that is involved in chromatin remodeling, and may additionally play a role in DNA damage response. The encoded protein functions as part of an ATP-dependent complex that is involved in neurulation. This gene is a candidate gene for Cat Eye Syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

ENSG00000286195 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 22-17549440-C-G is Pathogenic according to our data. Variant chr22-17549440-C-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 4073552.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.12824816). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CECR2	NM_001290047.2	c.4153C>G	p.Gln1385Glu	missense_variant	Exon 17 of 19	ENST00000262608.13	NP_001276976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CECR2	ENST00000262608.13	c.4153C>G	p.Gln1385Glu	missense_variant	Exon 17 of 19	1	NM_001290047.2	ENSP00000262608.11

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

CECR2-related neurodevelopmental disorder Pathogenic:1

Jul 28, 2025

Center for Statistical Genetics, Columbia University

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: research

de novo heterozygous variant confimed by whole exome sequencing -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	16
DANN	Benign	0.87
DEOGEN2	Benign	0.079	.;T;.;T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.48	N
LIST_S2	Uncertain	0.88	D;D;D;D
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	.;M;.;.
PhyloP100		2.6
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.90	N;.;.;.
REVEL	Benign	0.086
Sift	Benign	0.046	D;.;.;.
Sift4G	Benign	0.95	T;T;T;T
Polyphen		0.29	B;B;.;.
Vest4		0.22
MutPred		0.12		.;Gain of relative solvent accessibility (P = 0.1571);.;.;
MVP		0.37
ClinPred		0.17	T
GERP RS		5.3
Varity_R		0.094
gMVP		0.071
Mutation Taster		=98/2	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

hg19: chr22-18029130;