22-17542357-T-C

Position:

• chr22-17542357-T-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001290047.2(CECR2):​c.2214T>C​(p.His738His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0109 in 1,613,674 control chromosomes in the GnomAD database, including 115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0082 (7 hom., cov: 32)
  • Exomes 𝑓: 0.011 (108 hom.)
• Consequence: CECR2 NM_001290047.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0590

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

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 22-17542357-T-C is Benign according to our data. Variant chr22-17542357-T-C is described in ClinVar as [Benign]. Clinvar id is 774535.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.059 with no splicing effect.
• BS2: High AC in GnomAd4 at 1243 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CECR2	NM_001290047.2	c.2214T>C	p.His738His	synonymous_variant	16/19	ENST00000262608.13	NP_001276976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CECR2	ENST00000262608.13	c.2214T>C	p.His738His	synonymous_variant	16/19	1	NM_001290047.2	ENSP00000262608.11

Frequencies

GnomAD3 genomes AF: 0.00817 AC: 1243 AN: 152130 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00548

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0102

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0120

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.00629 AC: 1552 AN: 246714 Hom.: 7 AF XY: 0.00621 AC XY: 835 AN XY: 134392

Gnomad AFR exome AF: 0.00509

Gnomad AMR exome AF: 0.00441

Gnomad ASJ exome AF: 0.000201

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00232

Gnomad FIN exome AF: 0.00177

Gnomad NFE exome AF: 0.0106

Gnomad OTH exome AF: 0.00599

GnomAD4 exome AF: 0.0112 AC: 16384 AN: 1461426 Hom.: 108 Cov.: 33 AF XY: 0.0107 AC XY: 7807 AN XY: 726982

Gnomad4 AFR exome AF: 0.00544

Gnomad4 AMR exome AF: 0.00541

Gnomad4 ASJ exome AF: 0.000306

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00206

Gnomad4 FIN exome AF: 0.00216

Gnomad4 NFE exome AF: 0.0135

Gnomad4 OTH exome AF: 0.0110

GnomAD4 genome AF: 0.00816 AC: 1243 AN: 152248 Hom.: 7 Cov.: 32 AF XY: 0.00731 AC XY: 544 AN XY: 74452

Gnomad4 AFR AF: 0.00546

Gnomad4 AMR AF: 0.0102

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00141

Gnomad4 NFE AF: 0.0120

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00989 Hom.: 12

Bravo AF: 0.00898

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0113

EpiControl AF: 0.0116

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
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.073
DANN	Benign	0.27

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: rs41277560; hg19: chr22-18022046;