rs596406

Variant names:

• chr10-11182702-T-C
• rs596406
• NM_001326342.2:c.271+17020T>C

Variant summary

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

The NM_001326342.2(CELF2):​c.271+17020T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,140 control chromosomes in the GnomAD database, including 2,466 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 0.14 (2466 hom., cov: 32)
• Consequence: CELF2 NM_001326342.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100
• Publications: 7 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELF2	NM_001326342.2	c.271+17020T>C		intron_variant	Intron 2 of 12	ENST00000633077.2	NP_001313271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELF2	ENST00000633077.2	c.271+17020T>C		intron_variant	Intron 2 of 12	1	NM_001326342.2	ENSP00000488690.1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21501 AN: 152020 Hom.: 2457 Cov.: 32

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0630

Gnomad ASJ AF: 0.0573

Gnomad EAS AF: 0.0358

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0840

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0797

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.142 AC: 21545 AN: 152140 Hom.: 2466 Cov.: 32 AF XY: 0.139 AC XY: 10308 AN XY: 74378

African (AFR) AF: 0.316 AC: 13105 AN: 41458

American (AMR) AF: 0.0628 AC: 959 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0573 AC: 199 AN: 3472

East Asian (EAS) AF: 0.0359 AC: 186 AN: 5178

South Asian (SAS) AF: 0.109 AC: 526 AN: 4826

European-Finnish (FIN) AF: 0.0840 AC: 892 AN: 10616

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0797 AC: 5420 AN: 67994

Other (OTH) AF: 0.114 AC: 241 AN: 2112

Alfa AF: 0.0941 Hom.: 1969

Bravo AF: 0.148

Asia WGS AF: 0.0930 AC: 326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.3
DANN	Benign	0.51
PhyloP100		0.0010
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs596406; hg19: chr10-11224665;