chr10-10846131-G-A

Variant names:

• chr10-10846131-G-A
• rs118184393
• NM_001326325.2:c.85G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001326325.2(CELF2):​c.85G>A​(p.Asp29Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00356 in 984,760 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/4 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0029 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0037 (6 hom.)
• Consequence: CELF2 NM_001326325.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.497
• Publications: 0 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 10-10846131-G-A is Benign according to our data. Variant chr10-10846131-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2640297.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 446 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELF2	NM_001326325.2	c.85G>A	p.Asp29Asn	missense_variant	Exon 2 of 16		NP_001313254.1
CELF2	XM_047424482.1	c.85G>A	p.Asp29Asn	missense_variant	Exon 2 of 16		XP_047280438.1
CELF2	XM_047424483.1	c.85G>A	p.Asp29Asn	missense_variant	Exon 2 of 16		XP_047280439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELF2	ENST00000638035.1	c.-81G>A		5_prime_UTR_variant	Exon 2 of 15	5		ENSP00000490401.1
CELF2	ENST00000637215.1	c.53+47314G>A		intron_variant	Intron 1 of 14	5		ENSP00000490185.1
CELF2	ENST00000636488.1	c.53+47314G>A		intron_variant	Intron 1 of 13	5		ENSP00000489955.1

Frequencies

GnomAD3 genomes AF: 0.00293 AC: 446 AN: 152020 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000556

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00859

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00397

Gnomad OTH AF: 0.00335

GnomAD4 exome AF: 0.00368 AC: 3060 AN: 832622 Hom.: 6 Cov.: 26 AF XY: 0.00359 AC XY: 1379 AN XY: 384544

African (AFR) AF: 0.000444 AC: 7 AN: 15780

American (AMR) AF: 0.00102 AC: 1 AN: 982

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5150

East Asian (EAS) AF: 0.00 AC: 0 AN: 3630

South Asian (SAS) AF: 0.00280 AC: 46 AN: 16444

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 276

Middle Eastern (MID) AF: 0.00309 AC: 5 AN: 1620

European-Non Finnish (NFE) AF: 0.00385 AC: 2928 AN: 761464

Other (OTH) AF: 0.00268 AC: 73 AN: 27276

GnomAD4 genome AF: 0.00293 AC: 446 AN: 152138 Hom.: 0 Cov.: 32 AF XY: 0.00292 AC XY: 217 AN XY: 74388

African (AFR) AF: 0.000554 AC: 23 AN: 41514

American (AMR) AF: 0.00177 AC: 27 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.000581 AC: 3 AN: 5166

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4818

European-Finnish (FIN) AF: 0.00859 AC: 91 AN: 10592

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00397 AC: 270 AN: 67996

Other (OTH) AF: 0.00331 AC: 7 AN: 2112

Alfa AF: 0.000366 Hom.: 0

Bravo AF: 0.00253

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CELF2: BS1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.77
PhyloP100		-0.50

Splicing

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

Other links and lift over

dbSNP: rs118184393; hg19: chr10-10888094;