dbSNP rs1386563271: FGF2:p.Gly125Glu (chr4-122827149-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_002006.6(FGF2):c.374G>A(p.Gly125Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,385,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000047 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

FGF2
NM_002006.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.709

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16025689).

BS2

High AC in GnomAd4 at 7 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002006.6. 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
	FGF2	NM_001361665.2	MANE Select	c.-26G>A		5_prime_UTR	Exon 1 of 3	NP_001348594.1	D9ZGF5
	FGF2	NM_002006.6		c.374G>A	p.Gly125Glu	missense	Exon 1 of 3	NP_001997.5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FGF2	ENST00000264498.9	TSL:1	c.374G>A	p.Gly125Glu	missense	Exon 1 of 3	ENSP00000264498.4	P09038-4
FGF2	ENST00000644866.2	MANE Select	c.-26G>A		5_prime_UTR	Exon 1 of 3	ENSP00000494222.1	P09038-2
FGF2	ENST00000608478.1	TSL:1	c.-26G>A		5_prime_UTR	Exon 1 of 3	ENSP00000477134.1	P09038-2

Frequencies

GnomAD3 genomes

AF:

0.0000467

AC:

AN:

149756

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

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:

0.0000897

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000190

AC:

AN:

52628

AF XY:

0.0000329

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000469

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000127

AC:

157

AN:

1235942

Hom.:

Cov.:

AF XY:

0.000105

AC XY:

AN XY:

601166

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25286

American (AMR)

AF:

0.00

AC:

AN:

18458

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19312

East Asian (EAS)

AF:

0.00

AC:

AN:

27424

South Asian (SAS)

AF:

0.00

AC:

AN:

55486

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35796

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3518

European-Non Finnish (NFE)

AF:

0.000155

AC:

155

AN:

1000318

Other (OTH)

AF:

0.0000397

AC:

AN:

50344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000467

AC:

AN:

149862

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

73074

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41320

American (AMR)

AF:

0.00

AC:

AN:

15130

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3418

East Asian (EAS)

AF:

0.00

AC:

AN:

5066

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9978

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000898

AC:

AN:

66848

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000142

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.41

CADD

Benign

7.9

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.33

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0097

LIST_S2

Benign

0.45

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.71

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

0.17

REVEL

Benign

0.11

Sift

Uncertain

0.0040

Sift4G

Benign

0.28

Polyphen

0.0

MutPred

0.24

Gain of solvent accessibility (P = 0.024)

MVP

0.30

ClinPred

0.079

GERP RS

-1.7

PromoterAI

-0.086

Neutral

(source)

Varity_R

0.044

gMVP

0.073

Mutation Taster

=299/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over