rs2399547

Variant names:

• chr10-10637075-A-G
• rs2399547
• NM_001326319.2:c.-132-45381A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-10637075-A-G
• chr10-10637075-A-T

Variant summary

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

The NM_001326319.2(CELF2):​c.-132-45381A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,020 control chromosomes in the GnomAD database, including 7,089 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 0.29 (7089 hom., cov: 31)
• Consequence: CELF2 NM_001326319.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.470
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001326319.2. 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.-132-45381A>G		intron	N/A	NP_001313248.1
	CELF2	NM_001326323.2		c.-188-45381A>G		intron	N/A	NP_001313252.1
	CELF2	NM_001326321.2		c.-94-45381A>G		intron	N/A	NP_001313250.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43712 AN: 151902 Hom.: 7093 Cov.: 31

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.0852

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.288 AC: 43720 AN: 152020 Hom.: 7089 Cov.: 31 AF XY: 0.286 AC XY: 21250 AN XY: 74288

African (AFR) AF: 0.166 AC: 6891 AN: 41488

American (AMR) AF: 0.282 AC: 4302 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 917 AN: 3470

East Asian (EAS) AF: 0.0852 AC: 440 AN: 5164

South Asian (SAS) AF: 0.159 AC: 767 AN: 4818

European-Finnish (FIN) AF: 0.410 AC: 4323 AN: 10536

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.369 AC: 25106 AN: 67958

Other (OTH) AF: 0.269 AC: 569 AN: 2112

Alfa AF: 0.334 Hom.: 17903

Bravo AF: 0.271

Asia WGS AF: 0.128 AC: 450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.4
DANN	Benign	0.71
PhyloP100		0.47

Splicing

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

Other links and lift over

dbSNP: rs2399547; hg19: chr10-10679038;