2-207767188-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PP3_StrongBS2

The NM_003468.4(FZD5):​c.1552G>A​(p.Gly518Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000874 in 1,601,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000090 ( 0 hom. )

Consequence

FZD5
NM_003468.4 missense

Scores

12
4
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.84
Variant links:
Genes affected
FZD5 (HGNC:4043): (frizzled class receptor 5) Members of the 'frizzled' gene family encode 7-transmembrane domain proteins that are receptors for Wnt signaling proteins. The FZD5 protein is believed to be the receptor for the Wnt5A ligand. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.94
BS2
High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FZD5NM_003468.4 linkc.1552G>A p.Gly518Ser missense_variant Exon 2 of 2 ENST00000295417.4 NP_003459.2 Q13467

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FZD5ENST00000295417.4 linkc.1552G>A p.Gly518Ser missense_variant Exon 2 of 2 1 NM_003468.4 ENSP00000354607.3 Q13467

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152234
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000444
AC:
1
AN:
225182
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
123146
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000101
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000897
AC:
13
AN:
1449640
Hom.:
0
Cov.:
31
AF XY:
0.00000833
AC XY:
6
AN XY:
720336
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000118
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000108
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152234
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74368
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.00000830
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Dec 08, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1552G>A (p.G518S) alteration is located in exon 2 (coding exon 1) of the FZD5 gene. This alteration results from a G to A substitution at nucleotide position 1552, causing the glycine (G) at amino acid position 518 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
Uncertain
0.52
BayesDel_addAF
Pathogenic
0.34
D
BayesDel_noAF
Pathogenic
0.24
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.80
D
Eigen
Pathogenic
0.76
Eigen_PC
Pathogenic
0.72
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Pathogenic
0.99
D
M_CAP
Pathogenic
0.38
D
MetaRNN
Pathogenic
0.94
D
MetaSVM
Uncertain
0.34
D
MutationAssessor
Uncertain
2.1
M
PrimateAI
Pathogenic
0.90
D
PROVEAN
Pathogenic
-5.7
D
REVEL
Pathogenic
0.84
Sift
Benign
0.14
T
Sift4G
Benign
0.11
T
Polyphen
1.0
D
Vest4
0.72
MutPred
0.85
Gain of MoRF binding (P = 0.1043);
MVP
0.87
ClinPred
0.99
D
GERP RS
4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.69
gMVP
0.86

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.

Other links and lift over

dbSNP: rs768441956; hg19: chr2-208631912; API