chr22-17542371-C-T

Variant names:

• chr22-17542371-C-T
• rs191800029
• NM_001290047.2:c.2228C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001290047.2(CECR2):​c.2228C>T​(p.Ala743Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000653 in 1,613,788 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0035 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00036 (7 hom.)
• Consequence: CECR2 NM_001290047.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.22
• 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005110383).
• BP6: Variant 22-17542371-C-T is Benign according to our data. Variant chr22-17542371-C-T is described in ClinVar as Benign. ClinVar VariationId is 731817.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 529 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290047.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CECR2	NM_001290047.2	MANE Select	c.2228C>T	p.Ala743Val	missense	Exon 16 of 19	NP_001276976.1	Q9BXF3-3
	CECR2	NM_001290046.2		c.1739C>T	p.Ala580Val	missense	Exon 16 of 19	NP_001276975.1	B7WPH3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CECR2	ENST00000262608.13	TSL:1 MANE Select	c.2228C>T	p.Ala743Val	missense	Exon 16 of 19	ENSP00000262608.11	Q9BXF3-3
	CECR2	ENST00000400585.7	TSL:1	c.1739C>T	p.Ala580Val	missense	Exon 16 of 19	ENSP00000383428.2	B7WPH3
	CECR2	ENST00000342247.10	TSL:5	c.2288C>T	p.Ala763Val	missense	Exon 17 of 20	ENSP00000341219.6	Q9BXF3-1

Frequencies

GnomAD3 genomes AF: 0.00346 AC: 527 AN: 152190 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0120

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00150

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: 0.0000294

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000943 AC: 233 AN: 246962 AF XY: 0.000736

Gnomad AFR exome AF: 0.0137

Gnomad AMR exome AF: 0.000638

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000359

Gnomad OTH exome AF: 0.000498

GnomAD4 exome AF: 0.000359 AC: 524 AN: 1461480 Hom.: 7 Cov.: 33 AF XY: 0.000297 AC XY: 216 AN XY: 727006

African (AFR) AF: 0.0126 AC: 423 AN: 33478

American (AMR) AF: 0.000671 AC: 30 AN: 44722

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53226

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

European-Non Finnish (NFE) AF: 0.0000243 AC: 27 AN: 1111840

Other (OTH) AF: 0.000629 AC: 38 AN: 60366

GnomAD4 genome AF: 0.00347 AC: 529 AN: 152308 Hom.: 4 Cov.: 32 AF XY: 0.00311 AC XY: 232 AN XY: 74480

African (AFR) AF: 0.0120 AC: 500 AN: 41550

American (AMR) AF: 0.00150 AC: 23 AN: 15310

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

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: 0.0000294 AC: 2 AN: 68030

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

Alfa AF: 0.00132 Hom.: 1

Bravo AF: 0.00432

ESP6500AA AF: 0.00909 AC: 34

ESP6500EA AF: 0.000122 AC: 1

ExAC AF: 0.00112 AC: 135

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	5.0
DANN	Benign	0.39
DEOGEN2	Benign	0.059	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.69	T
MetaRNN	Benign	0.0051	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.2
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.14
Sift	Benign	0.37	T
Sift4G	Benign	1.0	T
Polyphen		0.0080	B
Vest4		0.15
MVP		0.27
ClinPred		0.0070	T
GERP RS		4.4
Varity_R		0.018
gMVP		0.22
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: rs191800029; hg19: chr22-18022060;