rs10905838

Positions:

• chr10-10819442-G-A

Variant summary

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

The NM_001326325.2(CELF2):​c.16+22539G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0913 in 152,108 control chromosomes in the GnomAD database, including 745 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 0.091 (745 hom., cov: 32)
• Consequence: CELF2 NM_001326325.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CELF2	NM_001326317.2	c.-55-100522G>A		intron_variant			NP_001313246.1
CELF2	NM_001326318.2	c.-55-100522G>A		intron_variant			NP_001313247.1
CELF2	NM_001326319.2	c.-93-100522G>A		intron_variant			NP_001313248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CELF2	ENST00000636488.1	c.53+20625G>A		intron_variant		5		ENSP00000489955
CELF2	ENST00000637215.1	c.53+20625G>A		intron_variant		5		ENSP00000490185
CELF2	ENST00000638035.1	c.-150+20625G>A		intron_variant		5		ENSP00000490401

Frequencies

GnomAD3 genomes AF: 0.0911 AC: 13842 AN: 151990 Hom.: 743 Cov.: 32

Gnomad AFR AF: 0.0843

Gnomad AMI AF: 0.0253

Gnomad AMR AF: 0.0885

Gnomad ASJ AF: 0.0522

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0743

Gnomad OTH AF: 0.0829

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

GnomAD4 genome AF: 0.0913 AC: 13880 AN: 152108 Hom.: 745 Cov.: 32 AF XY: 0.0960 AC XY: 7139 AN XY: 74350

Gnomad4 AFR AF: 0.0849

Gnomad4 AMR AF: 0.0886

Gnomad4 ASJ AF: 0.0522

Gnomad4 EAS AF: 0.234

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.0743

Gnomad4 OTH AF: 0.0839

Alfa AF: 0.0800 Hom.: 264

Bravo AF: 0.0844

Asia WGS AF: 0.217 AC: 750 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.86
DANN	Benign	0.33

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10905838; hg19: chr10-10861405;