17-44557726-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001466.4(FZD2):c.38C>T(p.Pro13Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000958 in 1,599,778 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P13P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00079 ( 3 hom. )

Consequence

FZD2
NM_001466.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.493

Variant links:

Genes affected

FZD2 (HGNC:4040): (frizzled class receptor 2) This intronless gene is a member of the frizzled gene family. Members of this family encode seven-transmembrane domain proteins that are receptors for the wingless type MMTV integration site family of signaling proteins. This gene encodes a protein that is coupled to the beta-catenin canonical signaling pathway. Competition between the wingless-type MMTV integration site family, member 3A and wingless-type MMTV integration site family, member 5A gene products for binding of this protein is thought to regulate the beta-catenin-dependent and -independent pathways. [provided by RefSeq, Dec 2010]

FZD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0043268204).

BP6

Variant 17-44557726-C-T is Benign according to our data. Variant chr17-44557726-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 782157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 392 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FZD2	NM_001466.4 link	c.38C>T	p.Pro13Leu	missense_variant	Exon 1 of 1	ENST00000315323.5	NP_001457.1	Q14332Q86UZ8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FZD2	ENST00000315323.5 link	c.38C>T	p.Pro13Leu	missense_variant	Exon 1 of 1	6	NM_001466.4	ENSP00000323901.3		Q14332

Frequencies

GnomAD3 genomes

AF:

0.00258

AC:

392

AN:

151916

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00626

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00492

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.000648

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00114

AC:

246

AN:

216476

Hom.:

AF XY:

0.000977

AC XY:

116

AN XY:

118732

show subpopulations

Gnomad AFR exome

AF:

0.00553

Gnomad AMR exome

AF:

0.00272

Gnomad ASJ exome

AF:

0.000673

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000352

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000686

Gnomad OTH exome

AF:

0.00341

GnomAD4 exome

AF:

0.000787

AC:

1140

AN:

1447754

Hom.:

Cov.:

AF XY:

0.000750

AC XY:

540

AN XY:

720010

show subpopulations

Gnomad4 AFR exome

AF:

0.00789

Gnomad4 AMR exome

AF:

0.00325

Gnomad4 ASJ exome

AF:

0.000626

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000352

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000530

Gnomad4 OTH exome

AF:

0.00198

GnomAD4 genome

AF:

0.00258

AC:

392

AN:

152024

Hom.:

Cov.:

AF XY:

0.00249

AC XY:

185

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.00624

Gnomad4 AMR

AF:

0.00491

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000648

Gnomad4 OTH

AF:

0.00522

Alfa

AF:

0.00168

Hom.:

ExAC

AF:

0.00110

AC:

133

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 14, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

FZD2-related disorder

Benign:1

Sep 26, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.31

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.38

MetaRNN

Benign

0.0043

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.0

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

1.2

REVEL

Benign

0.085

Sift

Benign

0.24

Sift4G

Benign

0.67

Polyphen

0.0

Vest4

0.18

MVP

0.31

ClinPred

0.011

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Varity_R

0.036

gMVP

0.22

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.

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