10-10920007-C-T

Variant names:

• chr10-10920007-C-T
• rs577869156
• NM_001326325.2:c.146+8C>T

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.146+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000349 in 1,231,212 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 (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000032 (0 hom.)
• Consequence: CELF2 NM_001326325.2 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.271
• 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]

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

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 10-10920007-C-T is Benign according to our data. Variant chr10-10920007-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3910801.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELF2	NM_001326325.2	c.146+8C>T		splice_region_variant, intron_variant	Intron 3 of 15		NP_001313254.1
CELF2	NM_001326327.2	c.89+8C>T		splice_region_variant, intron_variant	Intron 2 of 14		NP_001313256.1
CELF2	NM_001326326.2	c.89+8C>T		splice_region_variant, intron_variant	Intron 2 of 14		NP_001313255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELF2	ENST00000637215.1	c.89+8C>T		splice_region_variant, intron_variant	Intron 2 of 14	5		ENSP00000490185.1
CELF2	ENST00000636488.1	c.89+8C>T		splice_region_variant, intron_variant	Intron 2 of 13	5		ENSP00000489955.1
CELF2	ENST00000638035.1	c.-20+8C>T		splice_region_variant, intron_variant	Intron 3 of 14	5		ENSP00000490401.1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000324 AC: 35 AN: 1078896 Hom.: 0 Cov.: 28 AF XY: 0.0000393 AC XY: 20 AN XY: 509312

African (AFR) AF: 0.00 AC: 0 AN: 22950

American (AMR) AF: 0.000119 AC: 1 AN: 8416

Ashkenazi Jewish (ASJ) AF: 0.0000695 AC: 1 AN: 14386

East Asian (EAS) AF: 0.00 AC: 0 AN: 26500

South Asian (SAS) AF: 0.000154 AC: 3 AN: 19488

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21100

Middle Eastern (MID) AF: 0.000343 AC: 1 AN: 2914

European-Non Finnish (NFE) AF: 0.0000272 AC: 25 AN: 919490

Other (OTH) AF: 0.0000916 AC: 4 AN: 43652

GnomAD4 genome AF: 0.0000525 AC: 8 AN: 152316 Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6 AN XY: 74476

African (AFR) AF: 0.00 AC: 0 AN: 41560

American (AMR) AF: 0.000131 AC: 2 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.075
DANN	Benign	0.78
PhyloP100		-0.27

Splicing

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

Other links and lift over

dbSNP: rs577869156; hg19: chr10-10961970;