Genetic Variant CWF19L2:p.Gly817Glu (chr11-107330009-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152434.3(CWF19L2):c.2450G>A(p.Gly817Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000071 in 1,408,188 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

CWF19L2
NM_152434.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.18

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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CWF19L2	NM_152434.3 link	c.2450G>A	p.Gly817Glu	missense_variant	Exon 17 of 18	ENST00000282251.10	NP_689647.2	Q2TBE0-1
CWF19L2	XM_047426419.1 link	c.1022G>A	p.Gly341Glu	missense_variant	Exon 10 of 11		XP_047282375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CWF19L2	ENST00000282251.10 link	c.2450G>A	p.Gly817Glu	missense_variant	Exon 17 of 18	1	NM_152434.3	ENSP00000282251.5		Q2TBE0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

179490

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.10e-7

AC:

AN:

1408188

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

696884

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31772

American (AMR)

AF:

0.00

AC:

AN:

35268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24770

East Asian (EAS)

AF:

0.00

AC:

AN:

37592

South Asian (SAS)

AF:

0.00

AC:

AN:

78234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51066

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5656

European-Non Finnish (NFE)

AF:

9.21e-7

AC:

AN:

1085514

Other (OTH)

AF:

0.00

AC:

AN:

58316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000283

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 13, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.2450G>A (p.G817E) alteration is located in exon 17 (coding exon 17) of the CWF19L2 gene. This alteration results from a G to A substitution at nucleotide position 2450, causing the glycine (G) at amino acid position 817 to be replaced by a glutamic acid (E). 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

Pathogenic

0.60

BayesDel_addAF

Benign

-0.068

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.038

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.77

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.60

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

6.2

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-7.5

REVEL

Uncertain

0.36

Sift

Uncertain

0.012

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.52

MVP

0.48

MPC

0.098

ClinPred

0.98

GERP RS

4.8

Varity_R

0.88

gMVP

0.76

Mutation Taster

=39/61

disease causing

(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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11-107330009-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over