rs1362939306

Variant names:

• chr4-122826999-G-A
• rs1362939306
• ENST00000264498.9:c.224G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

The NM_002006.6(FGF2):​c.224G>A​(p.Ser75Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00002 in 149,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.000020 (0 hom., cov: 31)
• Consequence: FGF2 NM_002006.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0520
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12734288).
• BP6: Variant 4-122826999-G-A is Benign according to our data. Variant chr4-122826999-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3278630.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002006.6. 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.-176G>A		5_prime_UTR	Exon 1 of 3	NP_001348594.1	D9ZGF5
	FGF2	NM_002006.6		c.224G>A	p.Ser75Asn	missense	Exon 1 of 3	NP_001997.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF2	ENST00000264498.9	TSL:1	c.224G>A	p.Ser75Asn	missense	Exon 1 of 3	ENSP00000264498.4	P09038-4
	FGF2	ENST00000644866.2	MANE Select	c.-176G>A		5_prime_UTR	Exon 1 of 3	ENSP00000494222.1	P09038-2
	FGF2	ENST00000608478.1	TSL:1	c.-176G>A		5_prime_UTR	Exon 1 of 3	ENSP00000477134.1	P09038-2

Frequencies

GnomAD3 genomes AF: 0.0000201 AC: 3 AN: 149568 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000588

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 1350 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.0000200 AC: 3 AN: 149674 Hom.: 0 Cov.: 31 AF XY: 0.0000137 AC XY: 1 AN XY: 73084

African (AFR) AF: 0.00 AC: 0 AN: 41244

American (AMR) AF: 0.00 AC: 0 AN: 15052

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3436

East Asian (EAS) AF: 0.000589 AC: 3 AN: 5090

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67172

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	11
DANN	Benign	0.96
DEOGEN2	Benign	0.34	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0073	N
LIST_S2	Benign	0.30	T
M_CAP	Pathogenic	0.32	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.052
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	0.050	N
REVEL	Uncertain	0.29
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.60	T
Polyphen		0.0	B
MVP		0.51
ClinPred		0.21	T
GERP RS		-0.13
PromoterAI		-0.024	Neutral
Varity_R		0.13
gMVP		0.013
Mutation Taster		=300/0	polymorphism

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: rs1362939306; hg19: chr4-123748154;