chr10-11288613-C-T

Variant names:

• chr10-11288613-C-T
• rs2277216
• NM_001326342.2:c.976+61C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001326342.2(CELF2):​c.976+61C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 1,588,636 control chromosomes in the GnomAD database, including 68,272 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.33 (8986 hom., cov: 32)
  • Exomes 𝑓: 0.28 (59286 hom.)
• Consequence: CELF2 NM_001326342.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.884
• Publications: 5 publications found

Genes affected

CELF2 (HGNC:2550): (CUGBP Elav-like family member 2) Members of the CELF/BRUNOL protein family contain two N-terminal RNA recognition motif (RRM) domains, one C-terminal RRM domain, and a divergent segment of 160-230 aa between the second and third RRM domains. Members of this protein family regulate pre-mRNA alternative splicing and may also be involved in mRNA editing, and translation. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

CELF2-AS1 (HGNC:23515): (CELF2 antisense RNA 1) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001326342.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELF2	NM_001326342.2	MANE Select	c.976+61C>T		intron	N/A	NP_001313271.1
	CELF2	NM_001326325.2		c.1048+61C>T		intron	N/A	NP_001313254.1
	CELF2	NM_001326343.2		c.976+61C>T		intron	N/A	NP_001313272.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELF2	ENST00000633077.2	TSL:1 MANE Select	c.976+61C>T		intron	N/A	ENSP00000488690.1
	CELF2	ENST00000632065.1	TSL:1	c.976+61C>T		intron	N/A	ENSP00000488422.1
	CELF2	ENST00000542579.5	TSL:1	c.976+61C>T		intron	N/A	ENSP00000443926.1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 50002 AN: 151886 Hom.: 8984 Cov.: 32

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.310

GnomAD4 exome AF: 0.281 AC: 403420 AN: 1436632 Hom.: 59286 AF XY: 0.283 AC XY: 201902 AN XY: 713310

African (AFR) AF: 0.452 AC: 14932 AN: 33008

American (AMR) AF: 0.351 AC: 14771 AN: 42120

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 5872 AN: 25328

East Asian (EAS) AF: 0.512 AC: 19826 AN: 38760

South Asian (SAS) AF: 0.378 AC: 31736 AN: 84024

European-Finnish (FIN) AF: 0.243 AC: 11787 AN: 48436

Middle Eastern (MID) AF: 0.282 AC: 1609 AN: 5710

European-Non Finnish (NFE) AF: 0.260 AC: 285704 AN: 1099762

Other (OTH) AF: 0.289 AC: 17183 AN: 59484

GnomAD4 genome AF: 0.329 AC: 50037 AN: 152004 Hom.: 8986 Cov.: 32 AF XY: 0.330 AC XY: 24547 AN XY: 74322

African (AFR) AF: 0.444 AC: 18370 AN: 41418

American (AMR) AF: 0.329 AC: 5030 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 785 AN: 3468

East Asian (EAS) AF: 0.547 AC: 2828 AN: 5166

South Asian (SAS) AF: 0.372 AC: 1797 AN: 4826

European-Finnish (FIN) AF: 0.253 AC: 2672 AN: 10568

Middle Eastern (MID) AF: 0.271 AC: 79 AN: 292

European-Non Finnish (NFE) AF: 0.259 AC: 17612 AN: 67968

Other (OTH) AF: 0.308 AC: 649 AN: 2108

Alfa AF: 0.276 Hom.: 6469

Bravo AF: 0.339

Asia WGS AF: 0.421 AC: 1461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.82
PhyloP100		-0.88
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: rs2277216; hg19: chr10-11330576; COSMIC: COSV59969624;