Genetic Variant ENST00000264498.9:c.271G>C (chr4-122827046-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000264498.9(FGF2):c.271G>C(p.Gly91Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000102 in 978,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000010 ( 0 hom. )

Consequence

FGF2
ENST00000264498.9 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.897

Variant links:

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]

FGF2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33236295).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF2	NM_001361665.2 link	c.-129G>C		5_prime_UTR_variant	Exon 1 of 3	ENST00000644866.2	NP_001348594.1
FGF2	NM_002006.6 link	c.271G>C	p.Gly91Arg	missense_variant	Exon 1 of 3		NP_001997.5	P09038-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FGF2	ENST00000264498.9 link	c.271G>C	p.Gly91Arg	missense_variant	Exon 1 of 3	1		ENSP00000264498.4	P09038-4A0A0A0MQV6
FGF2	ENST00000644866 link	c.-129G>C		5_prime_UTR_variant	Exon 1 of 3		NM_001361665.2	ENSP00000494222.1	P09038-2
FGF2	ENST00000608478 link	c.-129G>C		5_prime_UTR_variant	Exon 1 of 3	1		ENSP00000477134.1	P09038-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000102

AC:

AN:

978710

Hom.:

Cov.:

AF XY:

0.00000217

AC XY:

AN XY:

460196

show subpopulations

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:

0.0000538

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.033

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.33

.;T

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.53

T;T

M_CAP

Pathogenic

0.42

MetaRNN

Benign

0.33

T;T

MetaSVM

Benign

-0.61

MutationAssessor

Benign

0.55

.;N

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

0.18

N;.

REVEL

Uncertain

0.33

Sift

Uncertain

0.0030

D;.

Sift4G

Uncertain

0.0030

D;D

Polyphen

1.0

.;D

MutPred

0.44

Gain of methylation at G91 (P = 0.0042);Gain of methylation at G91 (P = 0.0042);

MVP

0.93

ClinPred

0.38

GERP RS

1.0

Varity_R

0.25

gMVP

0.089

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over