10-10920008-G-A

Variant names:

• chr10-10920008-G-A
• rs11256914
• NM_001326325.2:c.146+9G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001326325.2(CELF2):​c.146+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 1,228,752 control chromosomes in the GnomAD database, including 46,622 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (7556 hom., cov: 32)
  • Exomes 𝑓: 0.26 (39066 hom.)
• Consequence: CELF2 NM_001326325.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.12
• 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]

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 10-10920008-G-A is Benign according to our data. Variant chr10-10920008-G-A is described in ClinVar as [Benign]. Clinvar id is 769767.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELF2	NM_001326325.2	c.146+9G>A		intron_variant	Intron 3 of 15		NP_001313254.1
CELF2	NM_001326327.2	c.89+9G>A		intron_variant	Intron 2 of 14		NP_001313256.1
CELF2	NM_001326326.2	c.89+9G>A		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+9G>A		intron_variant	Intron 2 of 14	5		ENSP00000490185.1
CELF2	ENST00000636488.1	c.89+9G>A		intron_variant	Intron 2 of 13	5		ENSP00000489955.1
CELF2	ENST00000638035.1	c.-20+9G>A		intron_variant	Intron 3 of 14	5		ENSP00000490401.1

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45274 AN: 151940 Hom.: 7544 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.701

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.293

GnomAD4 exome AF: 0.257 AC: 276211 AN: 1076694 Hom.: 39066 Cov.: 29 AF XY: 0.257 AC XY: 130453 AN XY: 508354

African (AFR) AF: 0.286 AC: 6564 AN: 22918

American (AMR) AF: 0.487 AC: 4100 AN: 8416

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 3622 AN: 14372

East Asian (EAS) AF: 0.701 AC: 18582 AN: 26492

South Asian (SAS) AF: 0.330 AC: 6412 AN: 19426

European-Finnish (FIN) AF: 0.267 AC: 5622 AN: 21092

Middle Eastern (MID) AF: 0.267 AC: 778 AN: 2910

European-Non Finnish (NFE) AF: 0.238 AC: 218061 AN: 917490

Other (OTH) AF: 0.286 AC: 12470 AN: 43578

GnomAD4 genome AF: 0.298 AC: 45321 AN: 152058 Hom.: 7556 Cov.: 32 AF XY: 0.306 AC XY: 22746 AN XY: 74344

African (AFR) AF: 0.295 AC: 12243 AN: 41474

American (AMR) AF: 0.424 AC: 6475 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 887 AN: 3464

East Asian (EAS) AF: 0.701 AC: 3632 AN: 5178

South Asian (SAS) AF: 0.348 AC: 1678 AN: 4820

European-Finnish (FIN) AF: 0.285 AC: 3004 AN: 10548

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16480 AN: 67986

Other (OTH) AF: 0.300 AC: 633 AN: 2110

Alfa AF: 0.272 Hom.: 743

Bravo AF: 0.314

Asia WGS AF: 0.512 AC: 1781 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: 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	-0.80
CADD	Benign	4.8
DANN	Benign	0.70
PhyloP100		1.1

Splicing

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

Other links and lift over

dbSNP: rs11256914; hg19: chr10-10961971;