rs113537066

Variant names:

• chr4-122827273-C-T
• rs113537066
• NM_001361665.2:c.99C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001361665.2(FGF2):​c.99C>T​(p.Tyr33Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00048 in 1,612,904 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00050 (3 hom.)
• Consequence: FGF2 NM_001361665.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.26
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 4-122827273-C-T is Benign according to our data. Variant chr4-122827273-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 740852.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=3.26 with no splicing effect.
• BS2: High AC in GnomAd4 at 37 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001361665.2. 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.99C>T	p.Tyr33Tyr	synonymous	Exon 1 of 3	NP_001348594.1	D9ZGF5
	FGF2	NM_002006.6		c.498C>T	p.Tyr166Tyr	synonymous	Exon 1 of 3	NP_001997.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF2	ENST00000644866.2	MANE Select	c.99C>T	p.Tyr33Tyr	synonymous	Exon 1 of 3	ENSP00000494222.1	P09038-2
	FGF2	ENST00000264498.9	TSL:1	c.498C>T	p.Tyr166Tyr	synonymous	Exon 1 of 3	ENSP00000264498.4	P09038-4
	FGF2	ENST00000608478.1	TSL:1	c.99C>T	p.Tyr33Tyr	synonymous	Exon 1 of 3	ENSP00000477134.1	P09038-2

Frequencies

GnomAD3 genomes AF: 0.000243 AC: 37 AN: 152110 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000757

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000291 AC: 71 AN: 244150 AF XY: 0.000269

Gnomad AFR exome AF: 0.0000685

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000328

Gnomad NFE exome AF: 0.000475

Gnomad OTH exome AF: 0.000671

GnomAD4 exome AF: 0.000505 AC: 737 AN: 1460676 Hom.: 3 Cov.: 33 AF XY: 0.000497 AC XY: 361 AN XY: 726670

African (AFR) AF: 0.0000299 AC: 1 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.000209 AC: 18 AN: 86226

European-Finnish (FIN) AF: 0.000343 AC: 18 AN: 52428

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5764

European-Non Finnish (NFE) AF: 0.000604 AC: 672 AN: 1111896

Other (OTH) AF: 0.000431 AC: 26 AN: 60360

GnomAD4 genome AF: 0.000243 AC: 37 AN: 152228 Hom.: 0 Cov.: 31 AF XY: 0.000269 AC XY: 20 AN XY: 74444

African (AFR) AF: 0.0000241 AC: 1 AN: 41570

American (AMR) AF: 0.0000653 AC: 1 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.000757 AC: 8 AN: 10574

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000425 Hom.: 0

Bravo AF: 0.000193

EpiCase AF: 0.000545

EpiControl AF: 0.000474

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	12
DANN	Uncertain	0.98
PhyloP100		3.3
PromoterAI		0.043	Neutral
Mutation Taster		=33/67	disease causing

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

Other links and lift over

dbSNP: rs113537066; hg19: chr4-123748428;