Genetic Variant CWF19L2:p.Phe361Ser (chr11-107429150-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152434.3(CWF19L2):c.1082T>C(p.Phe361Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

CWF19L2
NM_152434.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.32

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.020320773).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CWF19L2	NM_152434.3 link	c.1082T>C	p.Phe361Ser	missense_variant	Exon 8 of 18	ENST00000282251.10	NP_689647.2	Q2TBE0-1
CWF19L2	XM_011542620.4 link	c.1082T>C	p.Phe361Ser	missense_variant	Exon 8 of 9		XP_011540922.1
CWF19L2	XR_007062452.1 link	n.1091T>C		non_coding_transcript_exon_variant	Exon 8 of 16
CWF19L2	XM_047426419.1 link	c.5+4484T>C		intron_variant	Intron 1 of 10		XP_047282375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CWF19L2	ENST00000282251.10 link	c.1082T>C	p.Phe361Ser	missense_variant	Exon 8 of 18	1	NM_152434.3	ENSP00000282251.5	Q2TBE0-1
CWF19L2	ENST00000431778.5 link	n.725T>C		non_coding_transcript_exon_variant	Exon 5 of 16	1		ENSP00000411736.1	H7C3G7
CWF19L2	ENST00000532251.1 link	n.725T>C		non_coding_transcript_exon_variant	Exon 5 of 15	1		ENSP00000434704.1	H0YE03

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000797

AC:

AN:

250926

AF XY:

0.00000737

show subpopulations

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:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461590

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727076

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111810

Other (OTH)

AF:

0.0000166

AC:

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 07, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1082T>C (p.F361S) alteration is located in exon 8 (coding exon 8) of the CWF19L2 gene. This alteration results from a T to C substitution at nucleotide position 1082, causing the phenylalanine (F) at amino acid position 361 to be replaced by a serine (S). 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

0.044

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.57

DEOGEN2

Benign

0.00027

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.31

M_CAP

Benign

0.0060

MetaRNN

Benign

0.020

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.0

PhyloP100

1.3

PrimateAI

Benign

0.23

PROVEAN

Benign

0.24

REVEL

Benign

0.055

Sift

Benign

0.70

Sift4G

Benign

0.42

Polyphen

0.0

Vest4

0.022

MutPred

0.14

Gain of phosphorylation at F361 (P = 0.069);

MVP

0.12

MPC

0.016

ClinPred

0.0093

GERP RS

-5.9

Varity_R

0.032

gMVP

0.24

Mutation Taster

=99/1

polymorphism

(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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11-107429150-A-G

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