Genetic Variant FZD2:p.Leu11_Leu12insMetPro (chr17-44557720-T-TGATGCC) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_001466.4(FZD2):c.33_34insATGCCG(p.Leu11_Leu12insMetPro) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000952 in 1,594,752 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00078 ( 3 hom. )

Consequence

FZD2
NM_001466.4 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.46

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP6

Variant 17-44557720-T-TGATGCC is Benign according to our data. Variant chr17-44557720-T-TGATGCC is described in ClinVar as [Benign]. Clinvar id is 782156.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.33_34insATGCCG	p.Leu11_Leu12insMetPro	conservative_inframe_insertion	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.33_34insATGCCG	p.Leu11_Leu12insMetPro	conservative_inframe_insertion	Exon 1 of 1	6	NM_001466.4	ENSP00000323901.3		Q14332

Frequencies

GnomAD3 genomes

AF:

0.00258

AC:

392

AN:

151956

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00625

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00491

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:

0.00526

GnomAD3 exomes

AF:

0.00105

AC:

229

AN:

217824

Hom.:

AF XY:

0.000901

AC XY:

108

AN XY:

119926

show subpopulations

Gnomad AFR exome

AF:

0.00501

Gnomad AMR exome

AF:

0.00257

Gnomad ASJ exome

AF:

0.000672

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000346

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000624

Gnomad OTH exome

AF:

0.00334

GnomAD4 exome

AF:

0.000781

AC:

1127

AN:

1442690

Hom.:

Cov.:

AF XY:

0.000742

AC XY:

532

AN XY:

717096

show subpopulations

Gnomad4 AFR exome

AF:

0.00771

Gnomad4 AMR exome

AF:

0.00328

Gnomad4 ASJ exome

AF:

0.000631

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000354

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000526

Gnomad4 OTH exome

AF:

0.00200

GnomAD4 genome

AF:

0.00258

AC:

392

AN:

152062

Hom.:

Cov.:

AF XY:

0.00249

AC XY:

185

AN XY:

74330

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:

0.00521

Alfa

AF:

0.00168

Hom.:

Asia WGS

AF:

0.000578

AC:

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FZD2: BS1, BS2 -

Jan 14, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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