rs2399547

Positions:

• chr10-10637075-A-G
• chr10-10637075-A-T

Variant summary

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

The NM_001326319.2(CELF2):​c.-132-45381A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,020 control chromosomes in the GnomAD database, including 7,089 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 0.29 (7089 hom., cov: 31)
• Consequence: CELF2 NM_001326319.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.470

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CELF2	NM_001326319.2	c.-132-45381A>G		intron_variant			NP_001313248.1
CELF2	NM_001326323.2	c.-188-45381A>G		intron_variant			NP_001313252.1
CELF2	NM_001326321.2	c.-94-45381A>G		intron_variant			NP_001313250.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43712 AN: 151902 Hom.: 7093 Cov.: 31

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.0852

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.288 AC: 43720 AN: 152020 Hom.: 7089 Cov.: 31 AF XY: 0.286 AC XY: 21250 AN XY: 74288

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.0852

Gnomad4 SAS AF: 0.159

Gnomad4 FIN AF: 0.410

Gnomad4 NFE AF: 0.369

Gnomad4 OTH AF: 0.269

Alfa AF: 0.343 Hom.: 12353

Bravo AF: 0.271

Asia WGS AF: 0.128 AC: 450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.4
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2399547; hg19: chr10-10679038;