Genetic Variant FGF2:c.282+5791C>T (chr4-122882215-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001361665.2(FGF2):c.282+5791C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,098 control chromosomes in the GnomAD database, including 2,411 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.16 ( 2411 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

FGF2
NM_001361665.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.33

Publications

5 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:

ENSG00000273007 (HGNC:):

ENSG00000273007 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
FGF2	NM_001361665.2 link	c.282+5791C>T	intron_variant	Intron 2 of 2	ENST00000644866.2	NP_001348594.1
LOC124900773	XR_007058262.1 link	n.1940G>A	non_coding_transcript_exon_variant	Exon 2 of 2
FGF2	NM_002006.6 link	c.681+5791C>T	intron_variant	Intron 2 of 2		NP_001997.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF2	ENST00000644866.2 link	c.282+5791C>T		intron_variant	Intron 2 of 2		NM_001361665.2	ENSP00000494222.1

Frequencies

GnomAD3 genomes

AF:

0.158

AC:

24068

AN:

151978

Hom.:

2411

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0577

Gnomad AMI

AF:

0.258

Gnomad AMR

AF:

0.175

Gnomad ASJ

AF:

0.192

Gnomad EAS

AF:

0.451

Gnomad SAS

AF:

0.366

Gnomad FIN

AF:

0.202

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.170

Gnomad OTH

AF:

0.141

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.158

AC:

24079

AN:

152098

Hom.:

2411

Cov.:

AF XY:

0.168

AC XY:

12492

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.0577

AC:

2396

AN:

41524

American (AMR)

AF:

0.176

AC:

2681

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.192

AC:

667

AN:

3466

East Asian (EAS)

AF:

0.451

AC:

2326

AN:

5158

South Asian (SAS)

AF:

0.366

AC:

1763

AN:

4812

European-Finnish (FIN)

AF:

0.202

AC:

2142

AN:

10584

Middle Eastern (MID)

AF:

0.122

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.170

AC:

11530

AN:

67968

Other (OTH)

AF:

0.144

AC:

303

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

980

1960

2940

3920

4900

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

290

580

870

1160

1450

<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:

0.175

Hom.:

1402

Bravo

AF:

0.145

Asia WGS

AF:

0.334

AC:

1161

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.28

(source)

DANN

Benign

0.38

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over