2-202035594-T-G

Variant names:

• chr2-202035594-T-G
• rs1171032851
• NM_003507.2:c.947T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003507.2(FZD7):​c.947T>G​(p.Val316Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V316A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FZD7 NM_003507.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.05
• Publications: 0 publications found

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]

ENSG00000296454 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.280361).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003507.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FZD7	NM_003507.2	MANE Select	c.947T>G	p.Val316Gly	missense	Exon 1 of 1	NP_003498.1	O75084

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FZD7	ENST00000286201.3	TSL:6 MANE Select	c.947T>G	p.Val316Gly	missense	Exon 1 of 1	ENSP00000286201.1	O75084
	ENSG00000296454	ENST00000739707.1		n.-45A>C		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	24
DANN	Benign	0.89
DEOGEN2	Benign	0.31	T
Eigen	Benign	-0.086
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	0.76	N
PhyloP100		4.0
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	0.74	N
REVEL	Uncertain	0.42
Sift	Benign	0.34	T
Sift4G	Benign	0.41	T
Polyphen		0.0010	B
Vest4		0.43
MutPred		0.59		Gain of disorder (P = 0.031)
MVP		0.96
MPC		1.3
ClinPred		0.67	D
GERP RS		5.0
Varity_R		0.52
gMVP		0.85
Mutation Taster		=70/30	polymorphism

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

Other links and lift over

dbSNP: rs1171032851; hg19: chr2-202900317;