2-207767060-G-A

Variant names:

• chr2-207767060-G-A
• rs58365448
• NM_003468.4:c.1680C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003468.4(FZD5):​c.1680C>T​(p.Ser560Ser) variant causes a synonymous change. The variant allele was found at a frequency of 0.00291 in 1,534,048 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (45 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (49 hom.)
• Consequence: FZD5 NM_003468.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 3.80
• Publications: 2 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 2-207767060-G-A is Benign according to our data. Variant chr2-207767060-G-A is described in ClinVar as Benign. ClinVar VariationId is 780859.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0544 is higher than 0.05.

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.1680C>T	p.Ser560Ser	synonymous	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.1680C>T	p.Ser560Ser	synonymous	Exon 2 of 2	ENSP00000354607.3	Q13467
	FZD5	ENST00000908573.1		c.1680C>T	p.Ser560Ser	synonymous	Exon 2 of 2	ENSP00000578632.1
	FZD5	ENST00000937374.1		c.1680C>T	p.Ser560Ser	synonymous	Exon 2 of 2	ENSP00000607433.1

Frequencies

GnomAD3 genomes AF: 0.0146 AC: 2217 AN: 152172 Hom.: 45 Cov.: 33

Gnomad AFR AF: 0.0496

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00746

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.00434 AC: 706 AN: 162540 AF XY: 0.00344

Gnomad AFR exome AF: 0.0597

Gnomad AMR exome AF: 0.00377

Gnomad ASJ exome AF: 0.000931

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000316

Gnomad OTH exome AF: 0.00325

GnomAD4 exome AF: 0.00163 AC: 2249 AN: 1381762 Hom.: 49 Cov.: 30 AF XY: 0.00148 AC XY: 1013 AN XY: 683866

African (AFR) AF: 0.0567 AC: 1628 AN: 28692

American (AMR) AF: 0.00395 AC: 123 AN: 31144

Ashkenazi Jewish (ASJ) AF: 0.000709 AC: 15 AN: 21142

East Asian (EAS) AF: 0.00 AC: 0 AN: 36952

South Asian (SAS) AF: 0.000149 AC: 11 AN: 73982

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45612

Middle Eastern (MID) AF: 0.00612 AC: 32 AN: 5230

European-Non Finnish (NFE) AF: 0.000166 AC: 180 AN: 1082226

Other (OTH) AF: 0.00458 AC: 260 AN: 56782

GnomAD4 genome AF: 0.0146 AC: 2219 AN: 152286 Hom.: 45 Cov.: 33 AF XY: 0.0144 AC XY: 1073 AN XY: 74462

African (AFR) AF: 0.0495 AC: 2058 AN: 41562

American (AMR) AF: 0.00745 AC: 114 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000324 AC: 22 AN: 68006

Other (OTH) AF: 0.00992 AC: 21 AN: 2116

Alfa AF: 0.00244 Hom.: 2

Bravo AF: 0.0172

Asia WGS AF: 0.00491 AC: 18 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	FZD5-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	8.4
DANN	Benign	0.96
PhyloP100		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs58365448; hg19: chr2-208631784;