11-107336569-T-G

Variant names:

• chr11-107336569-T-G
• rs373506062
• NM_152434.3:c.2347A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152434.3(CWF19L2):​c.2347A>C​(p.Ile783Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I783V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CWF19L2 NM_152434.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.07
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24338973).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CWF19L2	NM_152434.3	c.2347A>C	p.Ile783Leu	missense_variant	Exon 15 of 18	ENST00000282251.10	NP_689647.2
CWF19L2	XM_047426419.1	c.919A>C	p.Ile307Leu	missense_variant	Exon 8 of 11		XP_047282375.1
CWF19L2	XR_007062452.1	n.*58A>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CWF19L2	ENST00000282251.10	c.2347A>C	p.Ile783Leu	missense_variant	Exon 15 of 18	1	NM_152434.3	ENSP00000282251.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0059	T
Eigen	Benign	-0.061
Eigen_PC	Benign	0.073
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		5.1
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.12
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.038	D
Polyphen		0.20	B
Vest4		0.58
MutPred		0.47		Loss of methylation at K787 (P = 0.0532);
MVP		0.16
MPC		0.017
ClinPred		0.91	D
GERP RS		4.7
Varity_R		0.67
gMVP		0.65
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs373506062; hg19: chr11-107207295;