rs2146553

Variant names:

• chr10-10936303-G-A
• rs2146553
• ENST00000428520.7:n.688-890C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-10936303-G-A
• chr10-10936303-G-C
• chr10-10936303-G-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+16304G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 152,190 control chromosomes in the GnomAD database, including 35,460 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 0.67 (35460 hom., cov: 34)
• Consequence: CELF2 NM_001326325.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.680
• Publications: 2 publications found

Genes affected

LINC00710 (HGNC:27386): (long intergenic non-protein coding RNA 710)

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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001326325.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELF2	NM_001326325.2		c.146+16304G>A		intron	N/A	NP_001313254.1
	CELF2	NM_001326327.2		c.89+16304G>A		intron	N/A	NP_001313256.1	A0A1B0GUN8
	CELF2	NM_001326326.2		c.89+16304G>A		intron	N/A	NP_001313255.1	A0A1B0GU44

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINC00710	ENST00000428520.7	TSL:1	n.688-890C>T		intron	N/A
	LINC00710	ENST00000635670.2	TSL:1	n.548+321C>T		intron	N/A
	CELF2	ENST00000637215.1	TSL:5	c.89+16304G>A		intron	N/A	ENSP00000490185.1	A0A1B0GUN8

Frequencies

GnomAD3 genomes AF: 0.666 AC: 101207 AN: 152072 Hom.: 35405 Cov.: 34

Gnomad AFR AF: 0.854

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.922

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.673

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

GnomAD4 genome AF: 0.666 AC: 101317 AN: 152190 Hom.: 35460 Cov.: 34 AF XY: 0.670 AC XY: 49840 AN XY: 74390

African (AFR) AF: 0.854 AC: 35506 AN: 41554

American (AMR) AF: 0.744 AC: 11385 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.622 AC: 2160 AN: 3470

East Asian (EAS) AF: 0.922 AC: 4774 AN: 5178

South Asian (SAS) AF: 0.655 AC: 3159 AN: 4826

European-Finnish (FIN) AF: 0.589 AC: 6225 AN: 10564

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.530 AC: 36014 AN: 67984

Other (OTH) AF: 0.674 AC: 1421 AN: 2108

Alfa AF: 0.587 Hom.: 46835

Bravo AF: 0.690

Asia WGS AF: 0.792 AC: 2748 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.1
DANN	Benign	0.54
PhyloP100		0.68

Splicing

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

Other links and lift over

dbSNP: rs2146553; hg19: chr10-10978266;