10-10462995-C-T

Variant names:

• chr10-10462995-C-T
• rs2243539
• ENST00000684874.1:n.523C>T

Variant summary

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

The ENST00000684874.1(ENSG00000289328):​n.523C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 151,830 control chromosomes in the GnomAD database, including 26,462 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 0.59 (26462 hom., cov: 31)
• Consequence: ENSG00000289328 ENST00000684874.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.197
• Publications: 2 publications found

Genes affected

ENSG00000289328 (HGNC:):

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000684874.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELF2	NM_001326319.2		c.-133+409C>T		intron	N/A	NP_001313248.1
	CELF2	NM_001326323.2		c.-189+409C>T		intron	N/A	NP_001313252.1
	CELF2	NM_001326321.2		c.-95+409C>T		intron	N/A	NP_001313250.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000289328	ENST00000684874.1		n.523C>T		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.589 AC: 89405 AN: 151712 Hom.: 26434 Cov.: 31

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.588

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

GnomAD4 genome AF: 0.589 AC: 89478 AN: 151830 Hom.: 26462 Cov.: 31 AF XY: 0.592 AC XY: 43872 AN XY: 74168

African (AFR) AF: 0.581 AC: 24026 AN: 41358

American (AMR) AF: 0.658 AC: 10026 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.625 AC: 2169 AN: 3468

East Asian (EAS) AF: 0.573 AC: 2943 AN: 5138

South Asian (SAS) AF: 0.614 AC: 2951 AN: 4810

European-Finnish (FIN) AF: 0.605 AC: 6377 AN: 10548

Middle Eastern (MID) AF: 0.568 AC: 166 AN: 292

European-Non Finnish (NFE) AF: 0.576 AC: 39165 AN: 67948

Other (OTH) AF: 0.589 AC: 1245 AN: 2112

Alfa AF: 0.382 Hom.: 785

Bravo AF: 0.595

Asia WGS AF: 0.594 AC: 2066 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.69
PhyloP100		0.20

Splicing

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

Other links and lift over

dbSNP: rs2243539; hg19: chr10-10504958;