Genetic Variant CECR2:p.Gln1428Arg (chr22-17552036-A-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001290047.2(CECR2):c.4283A>G(p.Gln1428Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CECR2
NM_001290047.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.79

Publications

0 publications found

Variant links:

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]

CECR2 links:

ENSG00000286195 (HGNC:):

ENSG00000286195 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3319947).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CECR2	NM_001290047.2 link	c.4283A>G	p.Gln1428Arg	missense_variant	Exon 18 of 19	ENST00000262608.13	NP_001276976.1	Q9BXF3-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CECR2	ENST00000262608.13 link	c.4283A>G	p.Gln1428Arg	missense_variant	Exon 18 of 19	1	NM_001290047.2	ENSP00000262608.11		Q9BXF3-3A0A0R4J2E1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461614

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727092

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53386

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111800

Other (OTH)

AF:

0.00

AC:

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CECR2-related neurodevelopmental disorder

Uncertain:1

Jul 28, 2025

Center for Statistical Genetics, Columbia University

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:research

Heterozygous variant of unknown inheritance. Variant was not seen in one unaffected sibling that was tested -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

.;T;.;T

Eigen

Benign

0.065

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.78

T;T;T;T

M_CAP

Benign

0.0093

MetaRNN

Benign

0.33

T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.2

.;M;.;.

PhyloP100

3.8

PrimateAI

Benign

0.38

PROVEAN

Benign

-2.0

N;.;.;.

REVEL

Benign

0.076

Sift

Uncertain

0.0010

D;.;.;.

Sift4G

Uncertain

0.013

D;D;D;D

Polyphen

0.36

B;P;.;.

Vest4

0.55

MutPred

0.17

.;Gain of MoRF binding (P = 0.0193);.;.;

MVP

0.50

ClinPred

0.93

GERP RS

4.8

Varity_R

0.037

gMVP

0.14

Mutation Taster

=98/2

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over