2-202035874-G-A

Position:

• chr2-202035874-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_003507.2(FZD7):​c.1227G>A​(p.Gly409Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00143 in 1,614,158 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (3 hom.)
• Consequence: FZD7 NM_003507.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.13

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]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 2-202035874-G-A is Benign according to our data. Variant chr2-202035874-G-A is described in ClinVar as [Benign]. Clinvar id is 722432.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.13 with no splicing effect.
• BS2: High AC in GnomAd4 at 184 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FZD7	NM_003507.2	c.1227G>A	p.Gly409Gly	synonymous_variant	1/1	ENST00000286201.3	NP_003498.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FZD7	ENST00000286201.3	c.1227G>A	p.Gly409Gly	synonymous_variant	1/1	6	NM_003507.2	ENSP00000286201.1

Frequencies

GnomAD3 genomes AF: 0.00121 AC: 184 AN: 152226 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00320

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.000753

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00144

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00136 AC: 342 AN: 251390 Hom.: 2 AF XY: 0.00154 AC XY: 209 AN XY: 135888

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.00156

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.000489

Gnomad SAS exome AF: 0.00281

Gnomad FIN exome AF: 0.000740

Gnomad NFE exome AF: 0.00142

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00146 AC: 2130 AN: 1461814 Hom.: 3 Cov.: 33 AF XY: 0.00147 AC XY: 1067 AN XY: 727216

Gnomad4 AFR exome AF: 0.000388

Gnomad4 AMR exome AF: 0.00188

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.00318

Gnomad4 FIN exome AF: 0.000600

Gnomad4 NFE exome AF: 0.00144

Gnomad4 OTH exome AF: 0.00131

GnomAD4 genome AF: 0.00121 AC: 184 AN: 152344 Hom.: 0 Cov.: 33 AF XY: 0.00141 AC XY: 105 AN XY: 74490

Gnomad4 AFR AF: 0.000240

Gnomad4 AMR AF: 0.00320

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.00248

Gnomad4 FIN AF: 0.000753

Gnomad4 NFE AF: 0.00144

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.000793 Hom.: 0

Bravo AF: 0.00119

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00218

EpiControl AF: 0.00124

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	Jul 21, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	3.5
DANN	Benign	0.95

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

Other links and lift over

dbSNP: rs143927979; hg19: chr2-202900597;