chr22-17542187-C-A

Variant names:

• chr22-17542187-C-A
• rs200166225
• NM_001290047.2:c.2044C>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001290047.2(CECR2):​c.2044C>A​(p.Pro682Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000381 in 1,612,134 control chromosomes in the GnomAD database, including 2 homozygotes. 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 benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00026 (1 hom.)
• Consequence: CECR2 NM_001290047.2 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.65
• Publications: 3 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: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0041348934).
• BP6: Variant 22-17542187-C-A is Benign according to our data. Variant chr22-17542187-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 717121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 238 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CECR2	NM_001290047.2	c.2044C>A	p.Pro682Thr	missense_variant	Exon 16 of 19	ENST00000262608.13	NP_001276976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CECR2	ENST00000262608.13	c.2044C>A	p.Pro682Thr	missense_variant	Exon 16 of 19	1	NM_001290047.2	ENSP00000262608.11

Frequencies

GnomAD3 genomes AF: 0.00155 AC: 236 AN: 152182 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00502

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.000506 AC: 125 AN: 247150 AF XY: 0.000403

Gnomad AFR exome AF: 0.00585

Gnomad AMR exome AF: 0.000438

Gnomad ASJ exome AF: 0.000301

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000134

Gnomad OTH exome AF: 0.000499

GnomAD4 exome AF: 0.000258 AC: 377 AN: 1459834 Hom.: 1 Cov.: 33 AF XY: 0.000231 AC XY: 168 AN XY: 725858

African (AFR) AF: 0.00598 AC: 200 AN: 33446

American (AMR) AF: 0.000359 AC: 16 AN: 44562

Ashkenazi Jewish (ASJ) AF: 0.000230 AC: 6 AN: 26088

East Asian (EAS) AF: 0.00 AC: 0 AN: 39630

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86042

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53342

Middle Eastern (MID) AF: 0.00173 AC: 10 AN: 5764

European-Non Finnish (NFE) AF: 0.000101 AC: 112 AN: 1110678

Other (OTH) AF: 0.000531 AC: 32 AN: 60282

GnomAD4 genome AF: 0.00156 AC: 238 AN: 152300 Hom.: 1 Cov.: 32 AF XY: 0.00145 AC XY: 108 AN XY: 74480

African (AFR) AF: 0.00505 AC: 210 AN: 41558

American (AMR) AF: 0.00105 AC: 16 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68040

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.000739 Hom.: 1

Bravo AF: 0.00178

ESP6500AA AF: 0.00504 AC: 20

ESP6500EA AF: 0.000120 AC: 1

ExAC AF: 0.000546 AC: 66

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	13
DANN	Benign	0.97
DEOGEN2	Benign	0.13	.;T;.;T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.084
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.73	T;T;T;T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.0041	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	.;L;.;.
PhyloP100		1.7
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.5	D;.;.;.
REVEL	Benign	0.041
Sift	Benign	0.12	T;.;.;.
Sift4G	Benign	0.080	T;D;T;D
Polyphen		0.0020	B;B;.;.
Vest4		0.22
MVP		0.37
ClinPred		0.0070	T
GERP RS		4.2
Varity_R		0.061
gMVP		0.26
Mutation Taster		=81/19	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: rs200166225; hg19: chr22-18021876;