rs1281232115

Variant names:

• chr2-207767002-C-A
• rs1281232115
• NM_003468.4:c.1738G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-207767002-C-A
• chr2-207767002-C-T

Variant summary

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

The NM_003468.4(FZD5):​c.1738G>T​(p.Val580Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000753 in 1,328,478 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. V580M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: FZD5 NM_003468.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.65
• Publications: 0 publications found

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

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=0.11056453).

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.1738G>T	p.Val580Leu	missense	Exon 2 of 2	NP_003459.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FZD5	ENST00000295417.4	TSL:1 MANE Select	c.1738G>T	p.Val580Leu	missense	Exon 2 of 2	ENSP00000354607.3	Q13467
	FZD5	ENST00000908573.1		c.1738G>T	p.Val580Leu	missense	Exon 2 of 2	ENSP00000578632.1
	FZD5	ENST00000937374.1		c.1738G>T	p.Val580Leu	missense	Exon 2 of 2	ENSP00000607433.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000748 AC: 1 AN: 133638 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000104

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.53e-7 AC: 1 AN: 1328478 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 655326

African (AFR) AF: 0.00 AC: 0 AN: 26016

American (AMR) AF: 0.00 AC: 0 AN: 21634

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18696

East Asian (EAS) AF: 0.0000297 AC: 1 AN: 33682

South Asian (SAS) AF: 0.00 AC: 0 AN: 64634

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47928

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5212

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1056436

Other (OTH) AF: 0.00 AC: 0 AN: 54240

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.0014
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	0.0	N
PhyloP100		3.6
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.18
Sift	Benign	0.14	T
Sift4G	Benign	0.66	T
Polyphen		0.0010	B
Vest4		0.23
MutPred		0.14		Gain of loop (P = 0.0312)
MVP		0.50
ClinPred		0.27	T
GERP RS		5.0
Varity_R		0.16
gMVP		0.48
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1281232115; hg19: chr2-208631726;