NM_001466.4:c.50_52dupTGC

Variant names:

• chr17-44557726-C-CGCT
• rs761743182
• NM_001466.4:c.50_52dupTGC

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001466.4(FZD2):​c.50_52dupTGC​(p.Leu17dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000111 in 1,447,762 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P18P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: FZD2 NM_001466.4 disruptive_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0100
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 16 AD gene.

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_52dupTGC	p.Leu17dup	disruptive_inframe_insertion	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_52dupTGC	p.Leu17dup	disruptive_inframe_insertion	Exon 1 of 1	ENSP00000323901.3	Q14332

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000462 AC: 1 AN: 216476 AF XY: 0.00000842

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000106

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000111 AC: 16 AN: 1447762 Hom.: 0 Cov.: 32 AF XY: 0.0000153 AC XY: 11 AN XY: 720012

African (AFR) AF: 0.0000307 AC: 1 AN: 32580

American (AMR) AF: 0.00 AC: 0 AN: 43696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25574

East Asian (EAS) AF: 0.00 AC: 0 AN: 38550

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85274

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4150

European-Non Finnish (NFE) AF: 0.0000127 AC: 14 AN: 1106568

Other (OTH) AF: 0.00 AC: 0 AN: 59738

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.010

Splicing

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

Other links and lift over

dbSNP: rs761743182; hg19: chr17-42635094;