Variant 11-107353625-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152434.3(CWF19L2):c.1984A>G(p.Ile662Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

CWF19L2
NM_152434.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.42

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16910219).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CWF19L2	NM_152434.3 linkuse as main transcript	c.1984A>G	p.Ile662Val	missense_variant	13/18	ENST00000282251.10
CWF19L2	XM_047426419.1 linkuse as main transcript	c.556A>G	p.Ile186Val	missense_variant	6/11
CWF19L2	XR_007062452.1 linkuse as main transcript	n.1993A>G		non_coding_transcript_exon_variant	13/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CWF19L2	ENST00000282251.10 linkuse as main transcript	c.1984A>G	p.Ile662Val	missense_variant	13/18	1	NM_152434.3	P1	Q2TBE0-1
CWF19L2	ENST00000431778.5 linkuse as main transcript	c.1627A>G	p.Ile543Val	missense_variant, NMD_transcript_variant	10/16	1
CWF19L2	ENST00000532251.1 linkuse as main transcript	c.1569A>G	p.Leu523=	synonymous_variant, NMD_transcript_variant	10/15	1
CWF19L2	ENST00000462890.1 linkuse as main transcript	n.106A>G		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000889

AC:

AN:

1461536

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727058

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

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

Aug 02, 2022

The c.1984A>G (p.I662V) alteration is located in exon 13 (coding exon 13) of the CWF19L2 gene. This alteration results from a A to G substitution at nucleotide position 1984, causing the isoleucine (I) at amino acid position 662 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

0.062

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.64

DEOGEN2

Benign

0.039

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.65

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.67

M_CAP

Benign

0.0048

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

MutationTaster

Benign

0.81

D;D

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.80

REVEL

Benign

0.050

Sift

Benign

0.12

Sift4G

Benign

0.12

Polyphen

0.28

Vest4

0.33

MutPred

0.63

Loss of methylation at K660 (P = 0.0919);

MVP

0.13

MPC

0.016

ClinPred

0.17

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.19

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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