rs201099

Variant names:

• chr10-10982596-A-G
• rs201099
• NM_001326325.2:c.146+62597A>G

Variant summary

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

The NM_001326325.2(CELF2):​c.146+62597A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,136 control chromosomes in the GnomAD database, including 11,534 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 (11534 hom., cov: 31)
• Consequence: CELF2 NM_001326325.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.62
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELF2	NM_001326325.2	c.146+62597A>G		intron_variant	Intron 3 of 15		NP_001313254.1
CELF2	NM_001326327.2	c.89+62597A>G		intron_variant	Intron 2 of 14		NP_001313256.1
CELF2	NM_001326326.2	c.89+62597A>G		intron_variant	Intron 2 of 14		NP_001313255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELF2	ENST00000637215.1	c.89+62597A>G		intron_variant	Intron 2 of 14	5		ENSP00000490185.1
CELF2	ENST00000636488.1	c.89+62597A>G		intron_variant	Intron 2 of 13	5		ENSP00000489955.1
CELF2	ENST00000638035.1	c.-20+62597A>G		intron_variant	Intron 3 of 14	5		ENSP00000490401.1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44587 AN: 152018 Hom.: 11498 Cov.: 31

Gnomad AFR AF: 0.696

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.0177

Gnomad SAS AF: 0.0780

Gnomad FIN AF: 0.0566

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.294 AC: 44687 AN: 152136 Hom.: 11534 Cov.: 31 AF XY: 0.282 AC XY: 21004 AN XY: 74402

African (AFR) AF: 0.696 AC: 28861 AN: 41444

American (AMR) AF: 0.226 AC: 3462 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 545 AN: 3470

East Asian (EAS) AF: 0.0178 AC: 92 AN: 5182

South Asian (SAS) AF: 0.0781 AC: 377 AN: 4830

European-Finnish (FIN) AF: 0.0566 AC: 601 AN: 10622

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9919 AN: 67984

Other (OTH) AF: 0.273 AC: 576 AN: 2108

Alfa AF: 0.191 Hom.: 7244

Bravo AF: 0.327

Asia WGS AF: 0.116 AC: 404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.092
DANN	Benign	0.78
PhyloP100		-2.6

Splicing

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

Other links and lift over

dbSNP: rs201099; hg19: chr10-11024559;