Variant 11-107336695-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_152434.3(CWF19L2):c.2221G>T(p.Val741Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,481,928 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000067 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000098 ( 1 hom. )

Consequence

CWF19L2
NM_152434.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.88

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:

CWF19L2 (HGNC:):

CWF19L2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.798

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CWF19L2	NM_152434.3 linkuse as main transcript	c.2221G>T	p.Val741Leu	missense_variant	15/18	ENST00000282251.10	NP_689647.2	Q2TBE0-1
CWF19L2	XM_047426419.1 linkuse as main transcript	c.793G>T	p.Val265Leu	missense_variant	8/11		XP_047282375.1
CWF19L2	XR_007062452.1 linkuse as main transcript	n.2307G>T		non_coding_transcript_exon_variant	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CWF19L2	ENST00000282251.10 linkuse as main transcript	c.2221G>T	p.Val741Leu	missense_variant	15/18	1	NM_152434.3	ENSP00000282251.5		Q2TBE0-1

Frequencies

GnomAD3 genomes

AF:

0.0000666

AC:

AN:

150258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000597

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:

0.000486

GnomAD4 exome

AF:

0.00000976

AC:

AN:

1331554

Hom.:

Cov.:

AF XY:

0.00000604

AC XY:

AN XY:

661814

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000366

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:

0.0000724

GnomAD4 genome

AF:

0.0000665

AC:

AN:

150374

Hom.:

Cov.:

AF XY:

0.0000682

AC XY:

AN XY:

73336

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000597

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:

0.000481

ExAC

AF:

0.0000167

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 12, 2024

The c.2221G>T (p.V741L) alteration is located in exon 15 (coding exon 15) of the CWF19L2 gene. This alteration results from a G to T substitution at nucleotide position 2221, causing the valine (V) at amino acid position 741 to be replaced by a leucine (L). 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

0.62

BayesDel_addAF

Benign

-0.045

BayesDel_noAF

Benign

-0.11

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.011

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.018

MetaRNN

Pathogenic

0.80

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.2

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.9

REVEL

Benign

0.25

Sift

Benign

0.068

Sift4G

Uncertain

0.055

Polyphen

0.88

Vest4

0.77

MutPred

0.78

Gain of phosphorylation at S739 (P = 0.2076);

MVP

0.30

MPC

0.067

ClinPred

0.91

GERP RS

4.6

Varity_R

0.54

gMVP

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over