10-11027575-C-A

Variant names:

• chr10-11027575-C-A
• rs913918
• NM_001326342.2:c.74+9412C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001326342.2(CELF2):​c.74+9412C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.738 in 152,082 control chromosomes in the GnomAD database, including 45,057 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 0.74 (45057 hom., cov: 32)
• Consequence: CELF2 NM_001326342.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.425
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy 97

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELF2	NM_001326342.2	c.74+9412C>A		intron_variant	Intron 1 of 12	ENST00000633077.2	NP_001313271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELF2	ENST00000633077.2	c.74+9412C>A		intron_variant	Intron 1 of 12	1	NM_001326342.2	ENSP00000488690.1

Frequencies

GnomAD3 genomes AF: 0.739 AC: 112259 AN: 151956 Hom.: 45062 Cov.: 32

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.886

Gnomad AMR AF: 0.814

Gnomad ASJ AF: 0.869

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.856

Gnomad FIN AF: 0.899

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.877

Gnomad OTH AF: 0.775

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

GnomAD4 genome AF: 0.738 AC: 112291 AN: 152082 Hom.: 45057 Cov.: 32 AF XY: 0.744 AC XY: 55325 AN XY: 74342

African (AFR) AF: 0.391 AC: 16181 AN: 41422

American (AMR) AF: 0.814 AC: 12444 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.869 AC: 3016 AN: 3472

East Asian (EAS) AF: 0.905 AC: 4674 AN: 5164

South Asian (SAS) AF: 0.856 AC: 4128 AN: 4822

European-Finnish (FIN) AF: 0.899 AC: 9527 AN: 10594

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.877 AC: 59633 AN: 67998

Other (OTH) AF: 0.773 AC: 1629 AN: 2108

Alfa AF: 0.824 Hom.: 28175

Bravo AF: 0.716

Asia WGS AF: 0.827 AC: 2873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.1
DANN	Benign	0.25
PhyloP100		0.42
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs913918; hg19: chr10-11069538;