NM_001290047.2:c.3189T>C

Variant names:

• chr22-17548476-T-C
• rs182143214
• NM_001290047.2:c.3189T>C

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.3189T>C​(p.Pro1063Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000504 in 1,613,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0028 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00027 (0 hom.)
• Consequence: CECR2 NM_001290047.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.89
• Publications: 0 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=-0.97).
• BP6: Variant 22-17548476-T-C is Benign according to our data. Variant chr22-17548476-T-C is described in ClinVar as [Benign]. Clinvar id is 777660.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.89 with no splicing effect.
• BS2: High AC in GnomAd4 at 421 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CECR2	NM_001290047.2	c.3189T>C	p.Pro1063Pro	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.3189T>C	p.Pro1063Pro	synonymous_variant	Exon 17 of 19	1	NM_001290047.2	ENSP00000262608.11

Frequencies

GnomAD3 genomes AF: 0.00277 AC: 421 AN: 152118 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00937

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.000626 AC: 156 AN: 249030 AF XY: 0.000540

Gnomad AFR exome AF: 0.00879

Gnomad AMR exome AF: 0.000464

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.000269 AC: 393 AN: 1461622 Hom.: 0 Cov.: 34 AF XY: 0.000239 AC XY: 174 AN XY: 727100

African (AFR) AF: 0.00980 AC: 328 AN: 33480

American (AMR) AF: 0.000514 AC: 23 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111812

Other (OTH) AF: 0.000563 AC: 34 AN: 60374

GnomAD4 genome AF: 0.00277 AC: 421 AN: 152236 Hom.: 0 Cov.: 31 AF XY: 0.00278 AC XY: 207 AN XY: 74430

African (AFR) AF: 0.00934 AC: 388 AN: 41544

American (AMR) AF: 0.00144 AC: 22 AN: 15288

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68006

Other (OTH) AF: 0.00473 AC: 10 AN: 2112

Alfa AF: 0.00109 Hom.: 2

Bravo AF: 0.00308

Asia WGS AF: 0.000577 AC: 2 AN: 3478

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

- -

Dec 31, 2019

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	-0.97
CADD	Benign	0.14
DANN	Benign	0.19
PhyloP100		-4.9
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: rs182143214; hg19: chr22-18028166;