Genetic Variant NM_001361665.2:c.*1349G>A (chr4-122893745-G-A) – 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.*1349G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 152,096 control chromosomes in the GnomAD database, including 15,851 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 0.41 ( 15846 hom., cov: 33)

Exomes 𝑓: 0.44 ( 5 hom. )

Consequence

FGF2
NM_001361665.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.190

Publications

19 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:

NUDT6 (HGNC:8053): (nudix hydrolase 6) This gene overlaps and lies on the opposite strand from FGF2 gene, and is thought to be the FGF2 antisense gene. The two genes are independently transcribed, and their expression shows an inverse relationship, suggesting that this antisense transcript may regulate FGF2 expression. This gene has also been shown to have hormone-regulatory and antiproliferative actions in the pituitary that are independent of FGF2 expression. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

NUDT6 links:

Genome browser will be placed here

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 (NFE) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
FGF2	NM_001361665.2 link	c.*1349G>A	3_prime_UTR_variant	Exon 3 of 3	ENST00000644866.2	NP_001348594.1
NUDT6	NM_007083.5 link	c.554-520C>T	intron_variant	Intron 4 of 4	ENST00000304430.10	NP_009014.2	P53370-1
FGF2	NM_002006.6 link	c.*1349G>A	3_prime_UTR_variant	Exon 3 of 3		NP_001997.5	P09038-4
NUDT6	NM_198041.3 link	c.47-520C>T	intron_variant	Intron 4 of 4		NP_932158.1	P53370-2B4DG76

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF2	ENST00000644866.2 link	c.*1349G>A		3_prime_UTR_variant	Exon 3 of 3		NM_001361665.2	ENSP00000494222.1		P09038-2
NUDT6	ENST00000304430.10 link	c.554-520C>T		intron_variant	Intron 4 of 4	1	NM_007083.5	ENSP00000306070.5		P53370-1

Frequencies

GnomAD3 genomes

AF:

0.413

AC:

62737

AN:

151942

Hom.:

15840

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.609

Gnomad AMR

AF:

0.480

Gnomad ASJ

AF:

0.456

Gnomad EAS

AF:

0.452

Gnomad SAS

AF:

0.251

Gnomad FIN

AF:

0.595

Gnomad MID

AF:

0.299

Gnomad NFE

AF:

0.557

Gnomad OTH

AF:

0.439

GnomAD4 exome

AF:

0.444

AC:

AN:

Hom.:

Cov.:

AF XY:

0.563

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.750

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.423

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

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:

0.413

AC:

62747

AN:

152060

Hom.:

15846

Cov.:

AF XY:

0.410

AC XY:

30484

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.111

AC:

4612

AN:

41508

American (AMR)

AF:

0.480

AC:

7335

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.456

AC:

1583

AN:

3468

East Asian (EAS)

AF:

0.452

AC:

2337

AN:

5174

South Asian (SAS)

AF:

0.251

AC:

1211

AN:

4822

European-Finnish (FIN)

AF:

0.595

AC:

6275

AN:

10538

Middle Eastern (MID)

AF:

0.295

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.557

AC:

37822

AN:

67960

Other (OTH)

AF:

0.441

AC:

931

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1623

3246

4869

6492

8115

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

556

1112

1668

2224

2780

<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:

0.508

Hom.:

34331

Bravo

AF:

0.397

Asia WGS

AF:

0.358

AC:

1246

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

4.0

(source)

DANN

Benign

0.34

PhyloP100

-0.19

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