22-17511843-T-G

Position:

• chr22-17511843-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001290047.2(CECR2):​c.901T>G​(p.Leu301Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00367 in 1,612,160 control chromosomes in the GnomAD database, including 187 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (97 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (90 hom.)
• Consequence: CECR2 NM_001290047.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.32

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017008781).
• BP6: Variant 22-17511843-T-G is Benign according to our data. Variant chr22-17511843-T-G is described in ClinVar as [Benign]. Clinvar id is 777644.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CECR2	NM_001290047.2	c.901T>G	p.Leu301Val	missense_variant	8/19	ENST00000262608.13	NP_001276976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CECR2	ENST00000262608.13	c.901T>G	p.Leu301Val	missense_variant	8/19	1	NM_001290047.2	ENSP00000262608	P2
CECR2	ENST00000400585.7	c.412T>G	p.Leu138Val	missense_variant	8/19	1		ENSP00000383428	A2
CECR2	ENST00000342247.10	c.901T>G	p.Leu301Val	missense_variant	8/20	5		ENSP00000341219	A2
CECR2	ENST00000612582.1	c.835T>G	p.Leu279Val	missense_variant	8/19	5		ENSP00000477529	A2

Frequencies

GnomAD3 genomes AF: 0.0200 AC: 3043 AN: 152088 Hom.: 98 Cov.: 32

Gnomad AFR AF: 0.0707

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.0158

GnomAD3 exomes AF: 0.00497 AC: 1236 AN: 248716 Hom.: 45 AF XY: 0.00359 AC XY: 484 AN XY: 134936

Gnomad AFR exome AF: 0.0700

Gnomad AMR exome AF: 0.00338

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000168

Gnomad OTH exome AF: 0.00233

GnomAD4 exome AF: 0.00197 AC: 2869 AN: 1459954 Hom.: 90 Cov.: 30 AF XY: 0.00170 AC XY: 1237 AN XY: 726234

Gnomad4 AFR exome AF: 0.0697

Gnomad4 AMR exome AF: 0.00363

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000163

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000738

Gnomad4 OTH exome AF: 0.00433

GnomAD4 genome AF: 0.0200 AC: 3046 AN: 152206 Hom.: 97 Cov.: 32 AF XY: 0.0196 AC XY: 1455 AN XY: 74416

Gnomad4 AFR AF: 0.0705

Gnomad4 AMR AF: 0.00458

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.0157

Alfa AF: 0.00271 Hom.: 20

Bravo AF: 0.0218

ESP6500AA AF: 0.0634 AC: 261

ESP6500EA AF: 0.000238 AC: 2

ExAC AF: 0.00610 AC: 738

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.000110

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Benign	0.060	.;T;.;T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.085
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.75	T;T;T;T
MetaRNN	Benign	0.0017	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	.;L;.;.
MutationTaster	Benign	0.86	N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.1	N;.;.;.
REVEL	Benign	0.021
Sift	Uncertain	0.021	D;.;.;.
Sift4G	Benign	0.46	T;T;T;T
Polyphen		0.085	B;B;.;.
Vest4		0.12
MVP		0.50
ClinPred		0.011	T
GERP RS		3.8
Varity_R		0.099
gMVP		0.11

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: rs61745636; hg19: chr22-17990875;