ENST00000264498.9:c.326G>A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4BP6

The ENST00000264498.9(FGF2):c.326G>A(p.Gly109Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000925 in 1,081,124 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 (no stars).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 9.2e-7 ( 0 hom. )

Consequence

FGF2
ENST00000264498.9 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.105

Publications

1 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36319542).

BP6

Variant 4-122827101-G-A is Benign according to our data. Variant chr4-122827101-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 207863.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF2	NM_001361665.2 link	c.-74G>A		5_prime_UTR_variant	Exon 1 of 3	ENST00000644866.2	NP_001348594.1
FGF2	NM_002006.6 link	c.326G>A	p.Gly109Asp	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.326G>A	p.Gly109Asp	missense_variant	Exon 1 of 3	1		ENSP00000264498.4	P09038-4A0A0A0MQV6
FGF2	ENST00000644866.2 link	c.-74G>A		5_prime_UTR_variant	Exon 1 of 3		NM_001361665.2	ENSP00000494222.1	P09038-2
FGF2	ENST00000608478.1 link	c.-74G>A		5_prime_UTR_variant	Exon 1 of 3	1		ENSP00000477134.1	P09038-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.25e-7

AC:

AN:

1081124

Hom.:

Cov.:

AF XY:

0.00000195

AC XY:

AN XY:

514006

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

21724

American (AMR)

AF:

0.00

AC:

AN:

7326

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13256

East Asian (EAS)

AF:

0.00

AC:

AN:

23916

South Asian (SAS)

AF:

0.0000385

AC:

AN:

25994

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22812

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2822

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

920580

Other (OTH)

AF:

0.00

AC:

AN:

42694

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Long QT syndrome

Benign:1

Medical Research Institute, Tokyo Medical and Dental University

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Uncertain

0.080

BayesDel_noAF

Benign

-0.12

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.36

.;T

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.073

LIST_S2

Benign

0.43

T;T

M_CAP

Pathogenic

0.71

MetaRNN

Benign

0.36

T;T

MetaSVM

Benign

-0.60

MutationAssessor

Benign

0.34

.;N

PhyloP100

-0.10

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.37

N;.

REVEL

Uncertain

0.36

Sift

Uncertain

0.0060

D;.

Sift4G

Uncertain

0.0090

D;D

Polyphen

0.99

.;D

MutPred

0.32

Gain of solvent accessibility (P = 0.0281);Gain of solvent accessibility (P = 0.0281);

MVP

0.80

ClinPred

0.83

GERP RS

2.1

PromoterAI

-0.051

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.23

gMVP

0.13

Mutation Taster

=289/11

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over