NM_001290047.2:c.2541C>T

Variant names:

• chr22-17542684-C-T
• rs114626178
• NM_001290047.2:c.2541C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001290047.2(CECR2):​c.2541C>T​(p.Ala847Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00434 in 1,613,994 control chromosomes in the GnomAD database, including 269 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (148 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (121 hom.)
• Consequence: CECR2 NM_001290047.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.443
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 22-17542684-C-T is Benign according to our data. Variant chr22-17542684-C-T is described in ClinVar as [Benign]. Clinvar id is 777645.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.443 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CECR2	NM_001290047.2	c.2541C>T	p.Ala847Ala	synonymous_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.2541C>T	p.Ala847Ala	synonymous_variant	Exon 16 of 19	1	NM_001290047.2	ENSP00000262608.11

Frequencies

GnomAD3 genomes AF: 0.0234 AC: 3555 AN: 152166 Hom.: 147 Cov.: 32

Gnomad AFR AF: 0.0820

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00628

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.0177

GnomAD2 exomes AF: 0.00582 AC: 1451 AN: 249288 AF XY: 0.00422

Gnomad AFR exome AF: 0.0820

Gnomad AMR exome AF: 0.00397

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000230

Gnomad OTH exome AF: 0.00248

GnomAD4 exome AF: 0.00235 AC: 3437 AN: 1461710 Hom.: 121 Cov.: 33 AF XY: 0.00203 AC XY: 1474 AN XY: 727136

African (AFR) AF: 0.0825 AC: 2763 AN: 33480

American (AMR) AF: 0.00425 AC: 190 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26136

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

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00503 AC: 29 AN: 5768

European-Non Finnish (NFE) AF: 0.000121 AC: 134 AN: 1111870

Other (OTH) AF: 0.00502 AC: 303 AN: 60374

GnomAD4 genome AF: 0.0234 AC: 3561 AN: 152284 Hom.: 148 Cov.: 32 AF XY: 0.0230 AC XY: 1711 AN XY: 74460

African (AFR) AF: 0.0819 AC: 3401 AN: 41524

American (AMR) AF: 0.00627 AC: 96 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.000367 AC: 25 AN: 68040

Other (OTH) AF: 0.0175 AC: 37 AN: 2112

Alfa AF: 0.00864 Hom.: 92

Bravo AF: 0.0255

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000296

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	-0.61
CADD	Benign	9.3
DANN	Benign	0.83
PhyloP100		-0.44
Mutation Taster		=100/0	polymorphism (auto)

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: rs114626178; hg19: chr22-18022373;