chr17-44557742-C-G

Variant names:

• chr17-44557742-C-G
• rs764033381
• NM_001466.4:c.54C>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_001466.4(FZD2):​c.54C>G​(p.Pro18Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000055 in 1,455,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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: 0.0000055 (0 hom.)
• Consequence: FZD2 NM_001466.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.669
• 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=-0.669 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 8 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.54C>G	p.Pro18Pro	synonymous	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.54C>G	p.Pro18Pro	synonymous	Exon 1 of 1	ENSP00000323901.3	Q14332

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000550 AC: 8 AN: 1455264 Hom.: 0 Cov.: 32 AF XY: 0.00000276 AC XY: 2 AN XY: 724028

African (AFR) AF: 0.00 AC: 0 AN: 32868

American (AMR) AF: 0.00 AC: 0 AN: 44476

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25932

East Asian (EAS) AF: 0.00 AC: 0 AN: 38942

South Asian (SAS) AF: 0.00 AC: 0 AN: 85982

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52792

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4300

European-Non Finnish (NFE) AF: 0.00000721 AC: 8 AN: 1109938

Other (OTH) AF: 0.00 AC: 0 AN: 60034

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.6
DANN	Benign	0.84
PhyloP100		-0.67
PromoterAI		0.046	Neutral
Mutation Taster		=100/0	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: rs764033381; hg19: chr17-42635110;