2-207767024-G-A

Variant names:

• chr2-207767024-G-A
• rs13416271
• NM_003468.4:c.1716C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_003468.4(FZD5):​c.1716C>T​(p.Pro572Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00249 in 1,478,440 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (49 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (36 hom.)
• Consequence: FZD5 NM_003468.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.127
• Publications: 4 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 2-207767024-G-A is Benign according to our data. Variant chr2-207767024-G-A is described in ClinVar as Benign. ClinVar VariationId is 767844.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.127 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0141 (2143/152206) while in subpopulation AFR AF = 0.0495 (2056/41566). AF 95% confidence interval is 0.0477. There are 49 homozygotes in GnomAd4. There are 983 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2143 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.1716C>T	p.Pro572Pro	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.1716C>T	p.Pro572Pro	synonymous	Exon 2 of 2	ENSP00000354607.3	Q13467
	FZD5	ENST00000908573.1		c.1716C>T	p.Pro572Pro	synonymous	Exon 2 of 2	ENSP00000578632.1
	FZD5	ENST00000937374.1		c.1716C>T	p.Pro572Pro	synonymous	Exon 2 of 2	ENSP00000607433.1

Frequencies

GnomAD3 genomes AF: 0.0140 AC: 2135 AN: 152096 Hom.: 49 Cov.: 33

Gnomad AFR AF: 0.0494

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00907

GnomAD2 exomes AF: 0.00339 AC: 429 AN: 126648 AF XY: 0.00249

Gnomad AFR exome AF: 0.0487

Gnomad AMR exome AF: 0.00268

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.000401

GnomAD4 exome AF: 0.00116 AC: 1540 AN: 1326234 Hom.: 36 Cov.: 30 AF XY: 0.00100 AC XY: 655 AN XY: 654280

African (AFR) AF: 0.0475 AC: 1238 AN: 26062

American (AMR) AF: 0.00286 AC: 63 AN: 21992

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18760

East Asian (EAS) AF: 0.00 AC: 0 AN: 33640

South Asian (SAS) AF: 0.0000308 AC: 2 AN: 64878

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45004

Middle Eastern (MID) AF: 0.000965 AC: 5 AN: 5180

European-Non Finnish (NFE) AF: 0.0000757 AC: 80 AN: 1056452

Other (OTH) AF: 0.00280 AC: 152 AN: 54266

GnomAD4 genome AF: 0.0141 AC: 2143 AN: 152206 Hom.: 49 Cov.: 33 AF XY: 0.0132 AC XY: 983 AN XY: 74408

African (AFR) AF: 0.0495 AC: 2056 AN: 41566

American (AMR) AF: 0.00392 AC: 60 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 67930

Other (OTH) AF: 0.00898 AC: 19 AN: 2116

Alfa AF: 0.00957 Hom.: 4

Bravo AF: 0.0153

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	9.7
DANN	Benign	0.94
PhyloP100		0.13
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	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: rs13416271; hg19: chr2-208631748; COSMIC: COSV54944790;