chr17-44560120-C-T

Variant names:

• chr17-44560120-C-T
• rs4792948
• NM_001466.4:c.*734C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001466.4(FZD2):​c.*734C>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 0.12 in 152,140 control chromosomes in the GnomAD database, including 1,144 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 0.12 (1144 hom., cov: 31)
• Consequence: FZD2 NM_001466.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.319
• Publications: 4 publications found

Genes affected

FZD2 (HGNC:4040): (frizzled class receptor 2) This intronless gene is a member of the frizzled gene family. Members of this family encode seven-transmembrane domain proteins that are receptors for the wingless type MMTV integration site family of signaling proteins. This gene encodes a protein that is coupled to the beta-catenin canonical signaling pathway. Competition between the wingless-type MMTV integration site family, member 3A and wingless-type MMTV integration site family, member 5A gene products for binding of this protein is thought to regulate the beta-catenin-dependent and -independent pathways. [provided by RefSeq, Dec 2010]

FZD2 Gene-Disease associations (from GenCC):

• autosomal dominant omodysplasia

  Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• autosomal dominant Robinow syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FZD2	NM_001466.4	c.*734C>T		3_prime_UTR_variant	Exon 1 of 1	ENST00000315323.5	NP_001457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FZD2	ENST00000315323.5	c.*734C>T		3_prime_UTR_variant	Exon 1 of 1	6	NM_001466.4	ENSP00000323901.3

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18209 AN: 152022 Hom.: 1142 Cov.: 31

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.0581

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.143

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.120 AC: 18213 AN: 152140 Hom.: 1144 Cov.: 31 AF XY: 0.121 AC XY: 8982 AN XY: 74360

African (AFR) AF: 0.103 AC: 4290 AN: 41518

American (AMR) AF: 0.137 AC: 2092 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 607 AN: 3470

East Asian (EAS) AF: 0.0580 AC: 301 AN: 5188

South Asian (SAS) AF: 0.158 AC: 761 AN: 4826

European-Finnish (FIN) AF: 0.142 AC: 1498 AN: 10558

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8076 AN: 68004

Other (OTH) AF: 0.140 AC: 296 AN: 2108

Alfa AF: 0.122 Hom.: 2114

Bravo AF: 0.118

Asia WGS AF: 0.102 AC: 355 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	12
DANN	Benign	0.77
PhyloP100		0.32

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4792948; hg19: chr17-42637488;