10-10958376-G-T

Variant names:

• chr10-10958376-G-T
• rs62209
• NM_001326325.2:c.146+38377G>T

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+38377G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 151,998 control chromosomes in the GnomAD database, including 12,175 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 0.32 (12175 hom., cov: 32)
• Consequence: CELF2 NM_001326325.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.639
• Publications: 15 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=-0.94).
• 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+38377G>T		intron_variant	Intron 3 of 15		NP_001313254.1
CELF2	NM_001326327.2	c.89+38377G>T		intron_variant	Intron 2 of 14		NP_001313256.1
CELF2	NM_001326326.2	c.89+38377G>T		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+38377G>T		intron_variant	Intron 2 of 14	5		ENSP00000490185.1
CELF2	ENST00000636488.1	c.89+38377G>T		intron_variant	Intron 2 of 13	5		ENSP00000489955.1
CELF2	ENST00000638035.1	c.-20+38377G>T		intron_variant	Intron 3 of 14	5		ENSP00000490401.1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48925 AN: 151880 Hom.: 12137 Cov.: 32

Gnomad AFR AF: 0.696

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.0959

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.0954

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.294

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

GnomAD4 genome AF: 0.322 AC: 49007 AN: 151998 Hom.: 12175 Cov.: 32 AF XY: 0.311 AC XY: 23094 AN XY: 74306

African (AFR) AF: 0.697 AC: 28840 AN: 41404

American (AMR) AF: 0.214 AC: 3274 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 917 AN: 3464

East Asian (EAS) AF: 0.0959 AC: 495 AN: 5162

South Asian (SAS) AF: 0.141 AC: 682 AN: 4824

European-Finnish (FIN) AF: 0.0954 AC: 1011 AN: 10598

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12869 AN: 67962

Other (OTH) AF: 0.289 AC: 610 AN: 2110

Alfa AF: 0.234 Hom.: 18062

Bravo AF: 0.350

Asia WGS AF: 0.140 AC: 487 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.44
DANN	Benign	0.64
PhyloP100		-0.64

Splicing

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

Other links and lift over

dbSNP: rs62209; hg19: chr10-11000339;