2-202036512-C-T

Position:

• chr2-202036512-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003507.2(FZD7):​c.*140C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 697,022 control chromosomes in the GnomAD database, including 28,217 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.27 (5990 hom., cov: 33)
  • Exomes 𝑓: 0.27 (22227 hom.)
• Consequence: FZD7 NM_003507.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FZD7	NM_003507.2	c.*140C>T		3_prime_UTR_variant	1/1	ENST00000286201.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FZD7	ENST00000286201.3	c.*140C>T		3_prime_UTR_variant	1/1		NM_003507.2	P1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41199 AN: 151930 Hom.: 5988 Cov.: 33

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.00597

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.271 AC: 147693 AN: 544974 Hom.: 22227 Cov.: 7 AF XY: 0.263 AC XY: 73800 AN XY: 280088

Gnomad4 AFR exome AF: 0.258

Gnomad4 AMR exome AF: 0.261

Gnomad4 ASJ exome AF: 0.171

Gnomad4 EAS exome AF: 0.00246

Gnomad4 SAS exome AF: 0.121

Gnomad4 FIN exome AF: 0.360

Gnomad4 NFE exome AF: 0.310

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.271 AC: 41230 AN: 152048 Hom.: 5990 Cov.: 33 AF XY: 0.268 AC XY: 19938 AN XY: 74294

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.261

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.00618

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.235

Alfa AF: 0.257 Hom.: 1753

Bravo AF: 0.263

Asia WGS AF: 0.0960 AC: 334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.14
DANN	Benign	0.61

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: rs13034206; hg19: chr2-202901235; COSMIC: COSV53811856; COSMIC: COSV53811856;