rs150027138

Variant names:

• chr17-44557726-C-G
• rs150027138
• NM_001466.4:c.38C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-44557726-C-G
• chr17-44557726-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001466.4(FZD2):​c.38C>G​(p.Pro13Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,447,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P13L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FZD2 NM_001466.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.493
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.118435025).

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.38C>G	p.Pro13Arg	missense	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.38C>G	p.Pro13Arg	missense	Exon 1 of 1	ENSP00000323901.3	Q14332

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1447762 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 720012

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

African (AFR) AF: 0.00 AC: 0 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: 0.00 AC: 0 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: 9.04e-7 AC: 1 AN: 1106568

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

⚠️ 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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	15
DANN	Benign	0.89
DEOGEN2	Benign	0.39	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.29	T
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.49
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.90	N
REVEL	Benign	0.12
Sift	Benign	0.10	T
Sift4G	Benign	0.36	T
Polyphen		0.032	B
Vest4		0.21
MutPred		0.50		Gain of MoRF binding (P = 9e-04)
MVP		0.39
ClinPred		0.060	T
GERP RS		2.4
PromoterAI		0.017	Neutral
Varity_R		0.066
gMVP		0.47
Mutation Taster		=87/13	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: rs150027138; hg19: chr17-42635094;