4-122827066-C-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The ENST00000264498.9(FGF2):c.291C>G(p.Gly97=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000422 in 1,112,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000061 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000039 (0 hom.)
• Consequence: FGF2 ENST00000264498.9 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.310

Genes affected

FGF2 (HGNC:3676): (fibroblast growth factor 2) The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members bind heparin and possess broad mitogenic and angiogenic activities. This protein has been implicated in diverse biological processes, such as limb and nervous system development, wound healing, and tumor growth. The mRNA for this gene contains multiple polyadenylation sites, and is alternatively translated from non-AUG (CUG) and AUG initiation codons, resulting in five different isoforms with distinct properties. The CUG-initiated isoforms are localized in the nucleus and are responsible for the intracrine effect, whereas, the AUG-initiated form is mostly cytosolic and is responsible for the paracrine and autocrine effects of this FGF. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 4-122827066-C-G is Benign according to our data. Variant chr4-122827066-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2672998.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.31 with no splicing effect.
• BS2: High AC in GnomAd at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGF2	NM_001361665.2	c.-109C>G		5_prime_UTR_variant	1/3	ENST00000644866.2
FGF2	NM_002006.6	c.291C>G	p.Gly97=	synonymous_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGF2	ENST00000264498.9	c.291C>G	p.Gly97=	synonymous_variant	1/3	1
FGF2	ENST00000644866.2	c.-109C>G		5_prime_UTR_variant	1/3		NM_001361665.2	P1
FGF2	ENST00000608478.1	c.-109C>G		5_prime_UTR_variant	1/3	1		P1

Frequencies

GnomAD3 genomes AF: 0.0000611 AC: 9 AN: 147318 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000734

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000905

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000394 AC: 38 AN: 965542 Hom.: 0 Cov.: 30 AF XY: 0.0000330 AC XY: 15 AN XY: 453986

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000449

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000611 AC: 9 AN: 147318 Hom.: 0 Cov.: 31 AF XY: 0.0000418 AC XY: 3 AN XY: 71702

Gnomad4 AFR AF: 0.0000734

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000905

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000567

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2023

FGF2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	17
Dann	Benign	0.93
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

LitVar

Other links and lift over

dbSNP: rs1237385877; hg19: chr4-123748221;