rs143595262

Variant names:

• chr22-17524110-C-G
• rs143595262
• NM_001290047.2:c.955-8C>G

Your query was ambiguous. Multiple possible variants found:

• chr22-17524110-C-G
• chr22-17524110-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001290047.2(CECR2):​c.955-8C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,425,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: CECR2 NM_001290047.2 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.270
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CECR2	NM_001290047.2	c.955-8C>G		splice_region_variant, intron_variant	Intron 8 of 18	ENST00000262608.13	NP_001276976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CECR2	ENST00000262608.13	c.955-8C>G		splice_region_variant, intron_variant	Intron 8 of 18	1	NM_001290047.2	ENSP00000262608.11

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1425062 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 705384

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32630

American (AMR) AF: 0.00 AC: 0 AN: 38284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25420

East Asian (EAS) AF: 0.00 AC: 0 AN: 37888

South Asian (SAS) AF: 0.00 AC: 0 AN: 81198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51080

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1093598

Other (OTH) AF: 0.0000169 AC: 1 AN: 59232

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.7
DANN	Benign	0.59
PhyloP100		-0.27

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: rs143595262; hg19: chr22-18003136;