chr22-17549256-G-A

Variant names:

• chr22-17549256-G-A
• rs146231898
• NM_001290047.2:c.3969G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001290047.2(CECR2):​c.3969G>A​(p.Pro1323Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000716 in 1,613,952 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0036 (4 hom., cov: 31)
  • Exomes 𝑓: 0.00042 (9 hom.)
• Consequence: CECR2 NM_001290047.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.08
• 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 22-17549256-G-A is Benign according to our data. Variant chr22-17549256-G-A is described in ClinVar as [Benign]. Clinvar id is 731818.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.08 with no splicing effect.
• BS2: High AC in GnomAd4 at 549 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CECR2	NM_001290047.2	c.3969G>A	p.Pro1323Pro	synonymous_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.3969G>A	p.Pro1323Pro	synonymous_variant	Exon 17 of 19	1	NM_001290047.2	ENSP00000262608.11

Frequencies

GnomAD3 genomes AF: 0.00361 AC: 549 AN: 152130 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.0126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00192

GnomAD2 exomes AF: 0.00103 AC: 256 AN: 249296 AF XY: 0.000799

Gnomad AFR exome AF: 0.0138

Gnomad AMR exome AF: 0.000811

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000796

Gnomad OTH exome AF: 0.000661

GnomAD4 exome AF: 0.000415 AC: 607 AN: 1461704 Hom.: 9 Cov.: 34 AF XY: 0.000337 AC XY: 245 AN XY: 727134

African (AFR) AF: 0.0125 AC: 420 AN: 33480

American (AMR) AF: 0.000783 AC: 35 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0000899 AC: 100 AN: 1111870

Other (OTH) AF: 0.000712 AC: 43 AN: 60372

GnomAD4 genome AF: 0.00361 AC: 549 AN: 152248 Hom.: 4 Cov.: 31 AF XY: 0.00322 AC XY: 240 AN XY: 74450

African (AFR) AF: 0.0125 AC: 520 AN: 41542

American (AMR) AF: 0.00144 AC: 22 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68022

Other (OTH) AF: 0.00190 AC: 4 AN: 2108

Alfa AF: 0.00148 Hom.: 4

Bravo AF: 0.00433

EpiCase AF: 0.0000545

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 10, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.21
DANN	Benign	0.49
PhyloP100		-1.1
Mutation Taster		=100/0	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: rs146231898; hg19: chr22-18028946; COSMIC: COSV52839376;