rs761743182

Variant names:

• chr17-44557726-CGCT-C
• rs761743182
• NM_001466.4:c.50_52delTGC

Your query was ambiguous. Multiple possible variants found:

• chr17-44557726-CGCT-C
• chr17-44557726-CGCT-CGCTGCT
• chr17-44557726-CGCT-CGCTGCTGCT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001466.4(FZD2):​c.50_52delTGC​(p.Leu17del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000138 in 1,447,354 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: FZD2 NM_001466.4 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.08
• Publications: 0 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: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• autosomal dominant Robinow syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001466.4. 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
	FZD2	NM_001466.4	MANE Select	c.50_52delTGC	p.Leu17del	disruptive_inframe_deletion	Exon 1 of 1	NP_001457.1	Q14332

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FZD2	ENST00000315323.5	TSL:6 MANE Select	c.50_52delTGC	p.Leu17del	disruptive_inframe_deletion	Exon 1 of 1	ENSP00000323901.3	Q14332

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.000111 AC: 24 AN: 216476 AF XY: 0.000109

Gnomad AFR exome AF: 0.000158

Gnomad AMR exome AF: 0.000126

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000191

Gnomad FIN exome AF: 0.0000521

Gnomad NFE exome AF: 0.000127

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000138 AC: 20 AN: 1447354 Hom.: 0 AF XY: 0.0000153 AC XY: 11 AN XY: 719786

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000307 AC: 1 AN: 32570

American (AMR) AF: 0.0000229 AC: 1 AN: 43666

Ashkenazi Jewish (ASJ) AF: 0.0000391 AC: 1 AN: 25566

East Asian (EAS) AF: 0.0000519 AC: 2 AN: 38526

South Asian (SAS) AF: 0.0000235 AC: 2 AN: 85226

European-Finnish (FIN) AF: 0.0000194 AC: 1 AN: 51592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4148

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1106336

Other (OTH) AF: 0.00 AC: 0 AN: 59724

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.000672 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.1
Mutation Taster		=69/31	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: rs761743182; hg19: chr17-42635094; COSMIC: COSV108130099;