dbSNP rs1463879546: FGF2:p.Arg112Gly (chr4-122827109-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_002006.6(FGF2):c.334C>G(p.Arg112Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000181 in 1,105,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000018 ( 0 hom. )

Consequence

FGF2
NM_002006.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.240

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 2 ACMG points.

PM1

In a modified_residue Symmetric dimethylarginine; alternate (size 0) in uniprot entity FGF2_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12111181).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF2	NM_001361665.2 link	c.-66C>G		5_prime_UTR_variant	Exon 1 of 3	ENST00000644866.2	NP_001348594.1
FGF2	NM_002006.6 link	c.334C>G	p.Arg112Gly	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.334C>G	p.Arg112Gly	missense_variant	Exon 1 of 3	1		ENSP00000264498.4	P09038-4A0A0A0MQV6
FGF2	ENST00000644866 link	c.-66C>G		5_prime_UTR_variant	Exon 1 of 3		NM_001361665.2	ENSP00000494222.1	P09038-2
FGF2	ENST00000608478 link	c.-66C>G		5_prime_UTR_variant	Exon 1 of 3	1		ENSP00000477134.1	P09038-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000181

AC:

AN:

1105194

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

527344

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000214

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

0.066

BayesDel_addAF

Uncertain

0.015

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.36

.;T

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.42

T;T

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.55

.;N

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.21

N;.

REVEL

Benign

0.15

Sift

Uncertain

0.0040

D;.

Sift4G

Uncertain

0.0050

D;D

Polyphen

0.017

.;B

MutPred

0.35

Loss of methylation at R112 (P = 7e-04);Loss of methylation at R112 (P = 7e-04);

MVP

0.41

ClinPred

0.31

GERP RS

-0.22

Varity_R

0.26

gMVP

0.21

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