10-11329048-T-TA

Position:

• chr10-11329048-T-TA

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PM4 PP5_Moderate

The NM_001326342.2(CELF2):​c.1562dup​(p.Tyr521Ter) variant causes a stop gained, frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CELF2 NM_001326342.2 stop_gained, frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 9.32

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:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Frameshift in the end of transcript resulting in stoplost. Downstream stopcodon found after 605 codons.
• PP5: Variant 10-11329048-T-TA is Pathogenic according to our data. Variant chr10-11329048-T-TA is described in ClinVar as [Pathogenic]. Clinvar id is 1299465.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CELF2	NM_001326342.2	c.1562dup	p.Tyr521Ter	stop_gained, frameshift_variant	13/13	ENST00000633077.2	NP_001313271.1
CELF2-AS1	NR_126062.1	n.98-5382_98-5381insT		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CELF2	ENST00000633077.2	c.1562dup	p.Tyr521Ter	stop_gained, frameshift_variant	13/13	1	NM_001326342.2	ENSP00000488690	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Developmental and epileptic encephalopathy 97 Pathogenic:2

Pathogenic, criteria provided, single submitter	clinical testing	Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	Nov 13, 2020	- -
Pathogenic, no assertion criteria provided	literature only	OMIM	Oct 06, 2021	- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-11371011;