10-11005437-T-C

Variant names:

• chr10-11005437-T-C
• rs200779130
• ENST00000416382.6:c.50T>C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Moderate BP6 BS2

The NM_001326336.2(CELF2):​c.50T>C​(p.Leu17Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000366 in 1,613,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00027 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00038 (0 hom.)
• Consequence: CELF2 NM_001326336.2 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 6.11
• 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: 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19939512).
• BP6: Variant 10-11005437-T-C is Benign according to our data. Variant chr10-11005437-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3048917.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 41 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001326336.2. 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_001326336.2		c.50T>C	p.Leu17Ser	missense	Exon 1 of 14	NP_001313265.1
	CELF2	NM_001326331.2		c.50T>C	p.Leu17Ser	missense	Exon 1 of 14	NP_001313260.1	A0A0J9YX66
	CELF2	NM_001394502.1		c.50T>C	p.Leu17Ser	missense	Exon 1 of 13	NP_001381431.1	A0A0J9YX66

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELF2	ENST00000416382.6	TSL:1	c.50T>C	p.Leu17Ser	missense	Exon 1 of 13	ENSP00000406451.2	O95319-1
	CELF2	ENST00000631816.1	TSL:2	c.50T>C	p.Leu17Ser	missense	Exon 1 of 14	ENSP00000488268.1	A0A0J9YX66
	CELF2	ENST00000631460.1	TSL:5	c.50T>C	p.Leu17Ser	missense	Exon 1 of 14	ENSP00000488582.1	O95319-1

Frequencies

GnomAD3 genomes AF: 0.000269 AC: 41 AN: 152202 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000221 AC: 55 AN: 249114 AF XY: 0.000200

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.000345

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000376 AC: 550 AN: 1461614 Hom.: 0 Cov.: 35 AF XY: 0.000380 AC XY: 276 AN XY: 727096

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.000134 AC: 6 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000359 AC: 31 AN: 86258

European-Finnish (FIN) AF: 0.0000749 AC: 4 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000444 AC: 494 AN: 1111796

Other (OTH) AF: 0.000248 AC: 15 AN: 60370

GnomAD4 genome AF: 0.000269 AC: 41 AN: 152202 Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14 AN XY: 74364

African (AFR) AF: 0.000145 AC: 6 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000470 AC: 32 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000397 Hom.: 0

Bravo AF: 0.000223

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000258 AC: 1

ESP6500EA AF: 0.000848 AC: 7

ExAC AF: 0.000240 AC: 29

EpiCase AF: 0.000218

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CELF2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	23
DANN	Benign	0.94
DEOGEN2	Benign	0.067	T
Eigen	Benign	-0.26
Eigen_PC	Benign	0.0016
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	0.55	N
PhyloP100		6.1
PROVEAN	Benign	0.12	N
REVEL	Uncertain	0.35
Sift	Benign	0.075	T
Sift4G	Benign	0.40	T
Polyphen		0.0080	B
Vest4		0.64
MVP		0.97
ClinPred		0.041	T
GERP RS		5.3
PromoterAI		-0.040	Neutral
Varity_R		0.10
Mutation Taster		=81/19	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs200779130; hg19: chr10-11047400;