chr10-10963741-G-A

Variant names:

• chr10-10963741-G-A
• rs201082
• NM_001326325.2:c.146+43742G>A

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+43742G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,124 control chromosomes in the GnomAD database, including 9,230 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 0.27 (9230 hom., cov: 32)
• Consequence: CELF2 NM_001326325.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.973
• Publications: 1 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

ENSG00000231496 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELF2	NM_001326325.2	c.146+43742G>A		intron_variant	Intron 3 of 15		NP_001313254.1
CELF2	NM_001326327.2	c.89+43742G>A		intron_variant	Intron 2 of 14		NP_001313256.1
CELF2	NM_001326326.2	c.89+43742G>A		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+43742G>A		intron_variant	Intron 2 of 14	5		ENSP00000490185.1
CELF2	ENST00000636488.1	c.89+43742G>A		intron_variant	Intron 2 of 13	5		ENSP00000489955.1
CELF2	ENST00000638035.1	c.-20+43742G>A		intron_variant	Intron 3 of 14	5		ENSP00000490401.1
ENSG00000231496	ENST00000420825.2	n.217-2821G>A		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41767 AN: 152006 Hom.: 9204 Cov.: 32

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.0956

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.0782

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.275 AC: 41832 AN: 152124 Hom.: 9230 Cov.: 32 AF XY: 0.264 AC XY: 19664 AN XY: 74376

African (AFR) AF: 0.615 AC: 25479 AN: 41446

American (AMR) AF: 0.174 AC: 2656 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 753 AN: 3472

East Asian (EAS) AF: 0.0959 AC: 496 AN: 5174

South Asian (SAS) AF: 0.116 AC: 558 AN: 4824

European-Finnish (FIN) AF: 0.0782 AC: 830 AN: 10614

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10350 AN: 67980

Other (OTH) AF: 0.242 AC: 512 AN: 2112

Alfa AF: 0.185 Hom.: 2014

Bravo AF: 0.300

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.7
DANN	Benign	0.23
PhyloP100		0.97

Splicing

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

Other links and lift over

dbSNP: rs201082; hg19: chr10-11005704;