Genetic Variant CWF19L2:p.Ile783Val (chr11-107336569-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_152434.3(CWF19L2):c.2347A>G(p.Ile783Val) variant causes a missense change. The variant allele was found at a frequency of 0.000102 in 1,601,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

CWF19L2
NM_152434.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.07

Publications

0 publications found

Variant links:

Genes affected

CWF19L2 (HGNC:26508): (CWF19 like cell cycle control factor 2) Predicted to be involved in mRNA splicing, via spliceosome. Predicted to be part of post-mRNA release spliceosomal complex. [provided by Alliance of Genome Resources, Apr 2022]

CWF19L2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1166513).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CWF19L2	NM_152434.3 link	c.2347A>G	p.Ile783Val	missense_variant	Exon 15 of 18	ENST00000282251.10	NP_689647.2	Q2TBE0-1
CWF19L2	XM_047426419.1 link	c.919A>G	p.Ile307Val	missense_variant	Exon 8 of 11		XP_047282375.1
CWF19L2	XR_007062452.1 link	n.*58A>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CWF19L2	ENST00000282251.10 link	c.2347A>G	p.Ile783Val	missense_variant	Exon 15 of 18	1	NM_152434.3	ENSP00000282251.5		Q2TBE0-1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000461

AC:

AN:

238616

AF XY:

0.0000544

show subpopulations

Gnomad AFR exome

AF:

0.000253

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000547

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000101

AC:

147

AN:

1449276

Hom.:

Cov.:

AF XY:

0.0000985

AC XY:

AN XY:

720490

show subpopulations

African (AFR)

AF:

0.0000306

AC:

AN:

32696

American (AMR)

AF:

0.00

AC:

AN:

41668

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25868

East Asian (EAS)

AF:

0.00

AC:

AN:

39392

South Asian (SAS)

AF:

0.0000362

AC:

AN:

82908

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53318

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

0.000128

AC:

142

AN:

1107790

Other (OTH)

AF:

0.0000167

AC:

AN:

59908

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000105

AC:

AN:

152284

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41562

American (AMR)

AF:

0.00

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000414

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000135

Hom.:

Bravo

AF:

0.0000907

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 20, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.2347A>G (p.I783V) alteration is located in exon 15 (coding exon 15) of the CWF19L2 gene. This alteration results from a A to G substitution at nucleotide position 2347, causing the isoleucine (I) at amino acid position 783 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0045

Eigen

Benign

-0.050

Eigen_PC

Benign

0.086

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.84

M_CAP

Benign

0.0073

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

PhyloP100

5.1

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.82

REVEL

Benign

0.095

Sift

Benign

0.053

Sift4G

Benign

0.078

Polyphen

0.045

Vest4

0.29

MVP

0.18

MPC

0.017

ClinPred

0.098

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.30

gMVP

0.54

Mutation Taster

=87/13

polymorphism

(source)

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

Publications

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11-107336569-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over