rs7099713

Variant names:

• chr10-11011180-A-C
• rs7099713
• ENST00000416382.6:c.53+5740A>C

Variant summary

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

The ENST00000416382.6(CELF2):​c.53+5740A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0656 in 152,220 control chromosomes in the GnomAD database, including 354 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 0.066 (354 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CELF2 ENST00000416382.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.595
• Publications: 2 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

CELF2-AS4 (HGNC:58359):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0772 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000416382.6. 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_001326325.2		c.146+91181A>C		intron	N/A	NP_001313254.1
	CELF2	NM_001326336.2		c.53+5740A>C		intron	N/A	NP_001313265.1
	CELF2	NM_001326327.2		c.89+91181A>C		intron	N/A	NP_001313256.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELF2	ENST00000416382.6	TSL:1	c.53+5740A>C		intron	N/A	ENSP00000406451.2
	CELF2	ENST00000637215.1	TSL:5	c.89+91181A>C		intron	N/A	ENSP00000490185.1
	CELF2	ENST00000636488.1	TSL:5	c.89+91181A>C		intron	N/A	ENSP00000489955.1

Frequencies

GnomAD3 genomes AF: 0.0656 AC: 9972 AN: 152102 Hom.: 353 Cov.: 31

Gnomad AFR AF: 0.0794

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.0618

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0224

Gnomad FIN AF: 0.0219

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0699

Gnomad OTH AF: 0.0751

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 8 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 6

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0656 AC: 9980 AN: 152220 Hom.: 354 Cov.: 31 AF XY: 0.0623 AC XY: 4638 AN XY: 74426

African (AFR) AF: 0.0795 AC: 3297 AN: 41492

American (AMR) AF: 0.0617 AC: 944 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 359 AN: 3472

East Asian (EAS) AF: 0.000770 AC: 4 AN: 5192

South Asian (SAS) AF: 0.0224 AC: 108 AN: 4820

European-Finnish (FIN) AF: 0.0219 AC: 232 AN: 10614

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.0699 AC: 4754 AN: 68006

Other (OTH) AF: 0.0743 AC: 157 AN: 2112

Alfa AF: 0.0701 Hom.: 322

Bravo AF: 0.0705

Asia WGS AF: 0.0130 AC: 44 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.7
DANN	Benign	0.67
PhyloP100		0.59
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs7099713; hg19: chr10-11053143;