Genetic Variant NM_003468.4:c.1563C>G (chr2-207767177-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_003468.4(FZD5):c.1563C>G(p.Ile521Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000762 in 1,443,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

FZD5
NM_003468.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.321

Publications

0 publications found

Variant links:

Genes affected

FZD5 (HGNC:4043): (frizzled class receptor 5) Members of the 'frizzled' gene family encode 7-transmembrane domain proteins that are receptors for Wnt signaling proteins. The FZD5 protein is believed to be the receptor for the Wnt5A ligand. [provided by RefSeq, Jul 2008]

FZD5 Gene-Disease associations (from GenCC):

microphthalmia/coloboma 11
Inheritance: AD Classification: STRONG Submitted by: G2P

FZD5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.936

BS2

High AC in GnomAdExome4 at 11 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003468.4. 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
	FZD5	NM_003468.4	MANE Select	c.1563C>G	p.Ile521Met	missense	Exon 2 of 2	NP_003459.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FZD5	ENST00000295417.4	TSL:1 MANE Select	c.1563C>G	p.Ile521Met	missense	Exon 2 of 2	ENSP00000354607.3	Q13467
FZD5	ENST00000908573.1		c.1563C>G	p.Ile521Met	missense	Exon 2 of 2	ENSP00000578632.1
FZD5	ENST00000937374.1		c.1563C>G	p.Ile521Met	missense	Exon 2 of 2	ENSP00000607433.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000762

AC:

AN:

1443790

Hom.:

Cov.:

AF XY:

0.00000976

AC XY:

AN XY:

717052

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32864

American (AMR)

AF:

0.00

AC:

AN:

42314

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25816

East Asian (EAS)

AF:

0.00

AC:

AN:

38300

South Asian (SAS)

AF:

0.00

AC:

AN:

84004

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00000996

AC:

AN:

1104392

Other (OTH)

AF:

0.00

AC:

AN:

59724

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.79

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.22

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.88

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.85

M_CAP

Pathogenic

0.48

MetaRNN

Pathogenic

0.94

MetaSVM

Uncertain

0.52

MutationAssessor

Pathogenic

3.5

PhyloP100

0.32

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-2.7

REVEL

Pathogenic

0.81

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.80

MutPred

0.73

Loss of catalytic residue at I521 (P = 0.008)

MVP

0.93

ClinPred

0.99

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.79

gMVP

0.87

Mutation Taster

=60/40

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over