rs17515365

Variant names:

• chr8-16992247-T-TA
• rs17515365
• NM_019851.3:c.*824dupT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_019851.3(FGF20):​c.*824dupT variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.179 in 152,080 control chromosomes in the GnomAD database, including 2,888 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.18 (2888 hom., cov: 28)
  • Failed GnomAD Quality Control
• Consequence: FGF20 NM_019851.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.91
• Publications: 1 publications found

Genes affected

FGF20 (HGNC:3677): (fibroblast growth factor 20) The protein encoded by this gene is a member of the fibroblast growth factor family. The fibroblast growth factors possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. This gene product is a secreted neurotrophic factor but lacks a typical signal peptide. It is expressed in normal brain, particularly the cerebellum, and may regulate central nervous system development and function. Homodimerization of this protein was shown to regulate its receptor binding activity and concentration gradient in the extracellular matrix. Genetic variations of this gene have been associated with Parkinson disease susceptibility. [provided by RefSeq, Oct 2009]

FGF20 Gene-Disease associations (from GenCC):

• bilateral renal agenesis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• renal hypodysplasia/aplasia 2

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF20	NM_019851.3	c.*824dupT		3_prime_UTR_variant	Exon 3 of 3	ENST00000180166.6	NP_062825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF20	ENST00000180166.6	c.*824dupT		3_prime_UTR_variant	Exon 3 of 3	1	NM_019851.3	ENSP00000180166.5

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27179 AN: 151962 Hom.: 2871 Cov.: 28

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.0626

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.0989

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.182

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.179 AC: 27231 AN: 152080 Hom.: 2888 Cov.: 28 AF XY: 0.180 AC XY: 13418 AN XY: 74358

African (AFR) AF: 0.221 AC: 9175 AN: 41508

American (AMR) AF: 0.238 AC: 3631 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 494 AN: 3470

East Asian (EAS) AF: 0.482 AC: 2482 AN: 5154

South Asian (SAS) AF: 0.226 AC: 1086 AN: 4810

European-Finnish (FIN) AF: 0.0989 AC: 1045 AN: 10568

Middle Eastern (MID) AF: 0.195 AC: 57 AN: 292

European-Non Finnish (NFE) AF: 0.130 AC: 8810 AN: 67984

Other (OTH) AF: 0.187 AC: 394 AN: 2110

Alfa AF: 0.150 Hom.: 223

Bravo AF: 0.192

Asia WGS AF: 0.329 AC: 1138 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.9
Mutation Taster		=100/0	polymorphism (auto)

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: rs17515365; hg19: chr8-16849756;