chr2-202035012-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_003507.2(FZD7):​c.365C>T​(p.Ser122Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000496 in 1,613,608 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: 0.0000048 ( 0 hom. )

Consequence

FZD7
NM_003507.2 missense

Scores

9
9
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.16
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.929
BS2
High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FZD7NM_003507.2 linkc.365C>T p.Ser122Phe 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
FZD7ENST00000286201.3 linkc.365C>T p.Ser122Phe missense_variant Exon 1 of 1 6 NM_003507.2 ENSP00000286201.1 O75084

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152270
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:
0.00000400
AC:
1
AN:
250100
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135336
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:
0.00000886
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461338
Hom.:
0
Cov.:
33
AF XY:
0.00000825
AC XY:
6
AN XY:
726994
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152270
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74392
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

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 14, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.365C>T (p.S122F) alteration is located in exon 1 (coding exon 1) of the FZD7 gene. This alteration results from a C to T substitution at nucleotide position 365, causing the serine (S) at amino acid position 122 to be replaced by a phenylalanine (F). 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
Pathogenic
0.78
BayesDel_addAF
Pathogenic
0.31
D
BayesDel_noAF
Pathogenic
0.21
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.75
D
Eigen
Pathogenic
0.81
Eigen_PC
Pathogenic
0.75
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.97
D
M_CAP
Uncertain
0.19
D
MetaRNN
Pathogenic
0.93
D
MetaSVM
Uncertain
0.57
D
MutationAssessor
Uncertain
2.9
M
PrimateAI
Pathogenic
0.80
T
PROVEAN
Pathogenic
-5.3
D
REVEL
Pathogenic
0.77
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.011
D
Polyphen
1.0
D
Vest4
0.85
MutPred
0.69
Loss of disorder (P = 0.1202);
MVP
0.89
MPC
2.2
ClinPred
1.0
D
GERP RS
5.3
Varity_R
0.90
gMVP
0.82

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: rs1020354758; hg19: chr2-202899735; API