rs2224693

chr10-10881888-T-Achr10-10881888-T-Cchr10-10881888-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001326325.2(CELF2):c.110+35732T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 152,114 control chromosomes in the GnomAD database, including 30,529 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 0.62 (30529 hom., cov: 32)
• Consequence: CELF2 NM_001326325.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.425

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.95 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CELF2	NM_001326317.2	c.-55-38076T>A		intron_variant
CELF2	NM_001326318.2	c.-55-38076T>A		intron_variant
CELF2	NM_001326319.2	c.-93-38076T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CELF2	ENST00000636488.1	c.54-38076T>A		intron_variant		5
CELF2	ENST00000637215.1	c.54-38076T>A		intron_variant		5
CELF2	ENST00000638035.1	c.-56+35732T>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93901 AN: 151998 Hom.: 30474 Cov.: 32

Gnomad AFR AF: 0.778

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.972

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.577

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.618 AC: 94017 AN: 152114 Hom.: 30529 Cov.: 32 AF XY: 0.626 AC XY: 46575 AN XY: 74360

Gnomad4 AFR AF: 0.779

Gnomad4 AMR AF: 0.626

Gnomad4 ASJ AF: 0.374

Gnomad4 EAS AF: 0.972

Gnomad4 SAS AF: 0.674

Gnomad4 FIN AF: 0.603

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.582

Alfa AF: 0.570 Hom.: 3170

Bravo AF: 0.627

Asia WGS AF: 0.838 AC: 2910 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	2.7
Dann	Benign	0.36

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2224693; hg19: chr10-10923851;