11-107334914-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_152434.3(CWF19L2):​c.2406G>T​(p.Leu802Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000373 in 1,607,674 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CWF19L2
NM_152434.3 missense

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.264
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.40067032).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CWF19L2NM_152434.3 linkc.2406G>T p.Leu802Phe missense_variant Exon 16 of 18 ENST00000282251.10 NP_689647.2 Q2TBE0-1
CWF19L2XM_047426419.1 linkc.978G>T p.Leu326Phe missense_variant Exon 9 of 11 XP_047282375.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CWF19L2ENST00000282251.10 linkc.2406G>T p.Leu802Phe missense_variant Exon 16 of 18 1 NM_152434.3 ENSP00000282251.5 Q2TBE0-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152168
Hom.:
0
Cov.:
33
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:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1455506
Hom.:
0
Cov.:
27
AF XY:
0.00000276
AC XY:
2
AN XY:
724446
show subpopulations
Gnomad4 AFR exome
AF:
0.0000600
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152168
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74318
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 18, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2406G>T (p.L802F) alteration is located in exon 16 (coding exon 16) of the CWF19L2 gene. This alteration results from a G to T substitution at nucleotide position 2406, causing the leucine (L) at amino acid position 802 to be replaced by a phenylalanine (F). 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
0.63
BayesDel_addAF
Benign
-0.086
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.071
T
Eigen
Uncertain
0.28
Eigen_PC
Benign
0.19
FATHMM_MKL
Benign
0.75
D
LIST_S2
Uncertain
0.95
D
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.40
T
MetaSVM
Benign
-0.96
T
MutationAssessor
Uncertain
2.5
M
PrimateAI
Uncertain
0.66
T
PROVEAN
Uncertain
-3.0
D
REVEL
Benign
0.28
Sift
Uncertain
0.0070
D
Sift4G
Uncertain
0.010
D
Polyphen
0.94
P
Vest4
0.55
MutPred
0.61
Gain of methylation at K801 (P = 0.0267);
MVP
0.37
MPC
0.10
ClinPred
0.98
D
GERP RS
0.59
Varity_R
0.44
gMVP
0.78

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs952516699; hg19: chr11-107205640; API