Variant 2-202035234-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_003507.2(FZD7):c.587G>A(p.Gly196Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00967 in 1,600,808 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0069 ( 7 hom., cov: 33)

Exomes 𝑓: 0.010 ( 87 hom. )

Consequence

FZD7
NM_003507.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.30

Variant links:

Genes affected

FZD7 (HGNC:4045): (frizzled class receptor 7) Members of the 'frizzled' gene family encode 7-transmembrane domain proteins that are receptors for Wnt signaling proteins. The FZD7 protein contains an N-terminal signal sequence, 10 cysteine residues typical of the cysteine-rich extracellular domain of Fz family members, 7 putative transmembrane domains, and an intracellular C-terminal tail with a PDZ domain-binding motif. FZD7 gene expression may downregulate APC function and enhance beta-catenin-mediated signals in poorly differentiated human esophageal carcinomas. [provided by RefSeq, Jul 2008]

FZD7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0064643323).

BP6

Variant 2-202035234-G-A is Benign according to our data. Variant chr2-202035234-G-A is described in ClinVar as [Benign]. Clinvar id is 770695.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1058 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FZD7	NM_003507.2 link	c.587G>A	p.Gly196Glu	missense_variant	Exon 1 of 1	ENST00000286201.3	NP_003498.1	O75084

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FZD7	ENST00000286201.3 link	c.587G>A	p.Gly196Glu	missense_variant	Exon 1 of 1	6	NM_003507.2	ENSP00000286201.1		O75084

Frequencies

GnomAD3 genomes

AF:

0.00690

AC:

1050

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00523

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.00641

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0120

Gnomad OTH

AF:

0.00716

GnomAD3 exomes

AF:

0.00751

AC:

1737

AN:

231432

Hom.:

AF XY:

0.00792

AC XY:

1012

AN XY:

127790

show subpopulations

Gnomad AFR exome

AF:

0.00171

Gnomad AMR exome

AF:

0.00424

Gnomad ASJ exome

AF:

0.00236

Gnomad EAS exome

AF:

0.00107

Gnomad SAS exome

AF:

0.00725

Gnomad FIN exome

AF:

0.00225

Gnomad NFE exome

AF:

0.0116

Gnomad OTH exome

AF:

0.00760

GnomAD4 exome

AF:

0.00996

AC:

14425

AN:

1448442

Hom.:

Cov.:

AF XY:

0.00990

AC XY:

7140

AN XY:

721070

show subpopulations

Gnomad4 AFR exome

AF:

0.00182

Gnomad4 AMR exome

AF:

0.00455

Gnomad4 ASJ exome

AF:

0.00253

Gnomad4 EAS exome

AF:

0.000580

Gnomad4 SAS exome

AF:

0.00783

Gnomad4 FIN exome

AF:

0.00217

Gnomad4 NFE exome

AF:

0.0115

Gnomad4 OTH exome

AF:

0.00857

GnomAD4 genome

AF:

0.00694

AC:

1058

AN:

152366

Hom.:

Cov.:

AF XY:

0.00651

AC XY:

485

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.00192

Gnomad4 AMR

AF:

0.00522

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.00642

Gnomad4 FIN

AF:

0.00122

Gnomad4 NFE

AF:

0.0120

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00923

Hom.:

Bravo

AF:

0.00634

TwinsUK

AF:

0.0146

AC:

ALSPAC

AF:

0.0138

AC:

ESP6500AA

AF:

0.000960

AC:

ESP6500EA

AF:

0.00733

AC:

ExAC

AF:

0.00756

AC:

906

Asia WGS

AF:

0.0320

AC:

111

AN:

3478

EpiCase

AF:

0.0103

EpiControl

AF:

0.0113

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.75

DEOGEN2

Benign

0.33

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.60

MetaRNN

Benign

0.0065

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.4

REVEL

Benign

0.24

Sift

Benign

0.15

Sift4G

Benign

0.64

Polyphen

0.21

Vest4

0.29

MVP

0.55

MPC

1.2

ClinPred

0.0046

GERP RS

3.7

Varity_R

0.11

gMVP

0.40

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