10-10846131-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2 BP4_Strong BP6_Moderate BS2

The NM_001326325.2(CELF2):c.85G>A(p.Asp29Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00356 in 984,760 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/4 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0029 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0037 (6 hom.)
• Consequence: CELF2 NM_001326325.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.497

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 -9 ACMG points.

• PP2: Missense variant where missense usually causes diseases, CELF2
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 10-10846131-G-A is Benign according to our data. Variant chr10-10846131-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2640297.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 446 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CELF2	NM_001326325.2	c.85G>A	p.Asp29Asn	missense_variant	2/16
CELF2	XM_047424482.1	c.85G>A	p.Asp29Asn	missense_variant	2/16
CELF2	XM_047424483.1	c.85G>A	p.Asp29Asn	missense_variant	2/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CELF2	ENST00000638035.1	c.-81G>A		5_prime_UTR_variant	2/15	5
CELF2	ENST00000636488.1	c.53+47314G>A		intron_variant		5
CELF2	ENST00000637215.1	c.53+47314G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00293 AC: 446 AN: 152020 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000556

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00859

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00397

Gnomad OTH AF: 0.00335

GnomAD4 exome AF: 0.00368 AC: 3060 AN: 832622 Hom.: 6 Cov.: 26 AF XY: 0.00359 AC XY: 1379 AN XY: 384544

Gnomad4 AFR exome AF: 0.000444

Gnomad4 AMR exome AF: 0.00102

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00280

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00385

Gnomad4 OTH exome AF: 0.00268

GnomAD4 genome AF: 0.00293 AC: 446 AN: 152138 Hom.: 0 Cov.: 32 AF XY: 0.00292 AC XY: 217 AN XY: 74388

Gnomad4 AFR AF: 0.000554

Gnomad4 AMR AF: 0.00177

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000581

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00859

Gnomad4 NFE AF: 0.00397

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.000366 Hom.: 0

Bravo AF: 0.00253

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

CELF2: BS1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.5
Dann	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs118184393; hg19: chr10-10888094;