NM_001290047.2:c.3000A>G

Variant names:

• chr22-17548287-A-G
• rs10427665
• NM_001290047.2:c.3000A>G

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.3000A>G​(p.Thr1000Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00415 in 1,608,588 control chromosomes in the GnomAD database, including 240 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (128 hom., cov: 31)
  • Exomes 𝑓: 0.0022 (112 hom.)
• Consequence: CECR2 NM_001290047.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.358
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 22-17548287-A-G is Benign according to our data. Variant chr22-17548287-A-G is described in ClinVar as [Benign]. Clinvar id is 777659.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.358 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CECR2	NM_001290047.2	c.3000A>G	p.Thr1000Thr	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.3000A>G	p.Thr1000Thr	synonymous_variant	Exon 17 of 19	1	NM_001290047.2	ENSP00000262608.11

Frequencies

GnomAD3 genomes AF: 0.0228 AC: 3468 AN: 152078 Hom.: 128 Cov.: 31

Gnomad AFR AF: 0.0802

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00629

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.0153

GnomAD2 exomes AF: 0.00533 AC: 1277 AN: 239548 AF XY: 0.00384

Gnomad AFR exome AF: 0.0785

Gnomad AMR exome AF: 0.00364

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000185

Gnomad OTH exome AF: 0.00254

GnomAD4 exome AF: 0.00220 AC: 3207 AN: 1456392 Hom.: 112 Cov.: 34 AF XY: 0.00191 AC XY: 1384 AN XY: 723958

African (AFR) AF: 0.0785 AC: 2610 AN: 33254

American (AMR) AF: 0.00394 AC: 173 AN: 43942

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26026

East Asian (EAS) AF: 0.00 AC: 0 AN: 39470

South Asian (SAS) AF: 0.000188 AC: 16 AN: 85268

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53086

Middle Eastern (MID) AF: 0.00417 AC: 24 AN: 5760

European-Non Finnish (NFE) AF: 0.0000883 AC: 98 AN: 1109390

Other (OTH) AF: 0.00475 AC: 286 AN: 60196

GnomAD4 genome AF: 0.0228 AC: 3474 AN: 152196 Hom.: 128 Cov.: 31 AF XY: 0.0221 AC XY: 1645 AN XY: 74422

African (AFR) AF: 0.0801 AC: 3325 AN: 41508

American (AMR) AF: 0.00628 AC: 96 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4812

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: 0.000279 AC: 19 AN: 68008

Other (OTH) AF: 0.0152 AC: 32 AN: 2108

Alfa AF: 0.00829 Hom.: 106

Bravo AF: 0.0251

Asia WGS AF: 0.00375 AC: 13 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	-1.0
CADD	Benign	0.26
DANN	Benign	0.31
PhyloP100		-0.36
Mutation Taster		=100/0	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: rs10427665; hg19: chr22-18027977;