dbSNP rs2922979: FGF2:c.178+109C>G (chr4-122827461-C-G) – 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.178+109C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 1,280,830 control chromosomes in the GnomAD database, including 81,409 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 0.43 ( 17028 hom., cov: 31)

Exomes 𝑓: 0.32 ( 64381 hom. )

Consequence

FGF2
NM_001361665.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.141

Publications

13 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF2	NM_001361665.2 link	c.178+109C>G		intron_variant	Intron 1 of 2	ENST00000644866.2	NP_001348594.1
FGF2	NM_002006.6 link	c.577+109C>G		intron_variant	Intron 1 of 2		NP_001997.5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
FGF2	ENST00000644866.2 link	c.178+109C>G	intron_variant	Intron 1 of 2		NM_001361665.2	ENSP00000494222.1
FGF2	ENST00000264498.9 link	c.577+109C>G	intron_variant	Intron 1 of 2	1		ENSP00000264498.4
FGF2	ENST00000608478.1 link	c.178+109C>G	intron_variant	Intron 1 of 2	1		ENSP00000477134.1

Frequencies

GnomAD3 genomes

AF:

0.428

AC:

64912

AN:

151832

Hom.:

16983

Cov.:

show subpopulations

Gnomad AFR

AF:

0.740

Gnomad AMI

AF:

0.275

Gnomad AMR

AF:

0.347

Gnomad ASJ

AF:

0.349

Gnomad EAS

AF:

0.160

Gnomad SAS

AF:

0.428

Gnomad FIN

AF:

0.221

Gnomad MID

AF:

0.405

Gnomad NFE

AF:

0.315

Gnomad OTH

AF:

0.407

GnomAD4 exome

AF:

0.323

AC:

364478

AN:

1128880

Hom.:

64381

AF XY:

0.326

AC XY:

185815

AN XY:

569726

show subpopulations

African (AFR)

AF:

0.757

AC:

19976

AN:

26376

American (AMR)

AF:

0.332

AC:

12575

AN:

37902

Ashkenazi Jewish (ASJ)

AF:

0.356

AC:

8338

AN:

23420

East Asian (EAS)

AF:

0.149

AC:

5278

AN:

35310

South Asian (SAS)

AF:

0.431

AC:

32371

AN:

75084

European-Finnish (FIN)

AF:

0.230

AC:

9895

AN:

43084

Middle Eastern (MID)

AF:

0.431

AC:

2210

AN:

5132

European-Non Finnish (NFE)

AF:

0.308

AC:

257059

AN:

833312

Other (OTH)

AF:

0.341

AC:

16776

AN:

49260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

11663

23326

34990

46653

58316

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7628

15256

22884

30512

38140

<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:

0.428

AC:

65019

AN:

151950

Hom.:

17028

Cov.:

AF XY:

0.420

AC XY:

31156

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.740

AC:

30678

AN:

41434

American (AMR)

AF:

0.348

AC:

5317

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.349

AC:

1212

AN:

3472

East Asian (EAS)

AF:

0.159

AC:

817

AN:

5126

South Asian (SAS)

AF:

0.427

AC:

2051

AN:

4804

European-Finnish (FIN)

AF:

0.221

AC:

2343

AN:

10592

Middle Eastern (MID)

AF:

0.408

AC:

120

AN:

294

European-Non Finnish (NFE)

AF:

0.315

AC:

21381

AN:

67924

Other (OTH)

AF:

0.404

AC:

851

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1618

3235

4853

6470

8088

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

570

1140

1710

2280

2850

<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:

0.381

Hom.:

1650

Bravo

AF:

0.449

Asia WGS

AF:

0.371

AC:

1289

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

8.0

(source)

DANN

Benign

0.56

PhyloP100

0.14

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over