NM_001290047.2:c.1777A>G

Variant names:

• chr22-17540693-A-G
• rs184360323
• NM_001290047.2:c.1777A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001290047.2(CECR2):​c.1777A>G​(p.Ser593Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00203 in 1,613,862 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0029 (11 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (85 hom.)
• Consequence: CECR2 NM_001290047.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.826
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0026817322).
• BP6: Variant 22-17540693-A-G is Benign according to our data. Variant chr22-17540693-A-G is described in ClinVar as [Benign]. Clinvar id is 788379.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CECR2	NM_001290047.2	c.1777A>G	p.Ser593Gly	missense_variant	Exon 14 of 19	ENST00000262608.13	NP_001276976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CECR2	ENST00000262608.13	c.1777A>G	p.Ser593Gly	missense_variant	Exon 14 of 19	1	NM_001290047.2	ENSP00000262608.11

Frequencies

GnomAD3 genomes AF: 0.00290 AC: 441 AN: 152230 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.000748

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0249

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00783 AC: 1948 AN: 248846 AF XY: 0.00583

Gnomad AFR exome AF: 0.000711

Gnomad AMR exome AF: 0.0542

Gnomad ASJ exome AF: 0.000398

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000928

Gnomad NFE exome AF: 0.000239

Gnomad OTH exome AF: 0.00564

GnomAD4 exome AF: 0.00194 AC: 2830 AN: 1461514 Hom.: 85 Cov.: 31 AF XY: 0.00164 AC XY: 1192 AN XY: 727032

African (AFR) AF: 0.000717 AC: 24 AN: 33480

American (AMR) AF: 0.0531 AC: 2373 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.000689 AC: 18 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.000394 AC: 34 AN: 86188

European-Finnish (FIN) AF: 0.000112 AC: 6 AN: 53400

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5766

European-Non Finnish (NFE) AF: 0.000228 AC: 253 AN: 1111796

Other (OTH) AF: 0.00187 AC: 113 AN: 60364

GnomAD4 genome AF: 0.00295 AC: 449 AN: 152348 Hom.: 11 Cov.: 32 AF XY: 0.00314 AC XY: 234 AN XY: 74510

African (AFR) AF: 0.000745 AC: 31 AN: 41590

American (AMR) AF: 0.0254 AC: 389 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 68036

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.000730 Hom.: 1

Bravo AF: 0.00487

ESP6500AA AF: 0.000765 AC: 3

ESP6500EA AF: 0.000242 AC: 2

ExAC AF: 0.00553 AC: 668

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	5.7
DANN	Benign	0.97
DEOGEN2	Benign	0.061	.;T;.;T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.56	T;T;T;T
MetaRNN	Benign	0.0027	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	.;M;.;.
PhyloP100		0.83
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.1	N;.;.;.
REVEL	Benign	0.0090
Sift	Uncertain	0.0030	D;.;.;.
Sift4G	Benign	0.13	T;T;T;T
Polyphen		0.43	B;B;.;.
Vest4		0.17
MVP		0.28
ClinPred		0.026	T
GERP RS		2.4
Varity_R		0.043
gMVP		0.24
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs184360323; hg19: chr22-18020382;