chr10-10559897-A-G

Variant names:

• chr10-10559897-A-G
• rs11256676
• NM_001326319.2:c.-133+97311A>G

Variant summary

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

The NM_001326319.2(CELF2):​c.-133+97311A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0801 in 152,196 control chromosomes in the GnomAD database, including 1,281 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 0.080 (1281 hom., cov: 32)
• Consequence: CELF2 NM_001326319.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.540
• Publications: 3 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELF2	NM_001326319.2	c.-133+97311A>G		intron_variant	Intron 1 of 16		NP_001313248.1
CELF2	NM_001326323.2	c.-189+97311A>G		intron_variant	Intron 1 of 17		NP_001313252.1
CELF2	NM_001326321.2	c.-95+97311A>G		intron_variant	Intron 1 of 15		NP_001313250.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.0798 AC: 12143 AN: 152078 Hom.: 1273 Cov.: 32

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0634

Gnomad ASJ AF: 0.00836

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.0132

Gnomad FIN AF: 0.0116

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00266

Gnomad OTH AF: 0.0603

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

GnomAD4 genome AF: 0.0801 AC: 12189 AN: 152196 Hom.: 1281 Cov.: 32 AF XY: 0.0797 AC XY: 5930 AN XY: 74406

African (AFR) AF: 0.240 AC: 9942 AN: 41488

American (AMR) AF: 0.0637 AC: 974 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00836 AC: 29 AN: 3468

East Asian (EAS) AF: 0.143 AC: 741 AN: 5172

South Asian (SAS) AF: 0.0128 AC: 62 AN: 4830

European-Finnish (FIN) AF: 0.0116 AC: 123 AN: 10608

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00266 AC: 181 AN: 68026

Other (OTH) AF: 0.0620 AC: 131 AN: 2112

Alfa AF: 0.0530 Hom.: 911

Bravo AF: 0.0898

Asia WGS AF: 0.0940 AC: 326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.6
DANN	Benign	0.36
PhyloP100		0.54

Splicing

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

Other links and lift over

dbSNP: rs11256676; hg19: chr10-10601860;