rs796052159

Variant names:

• chr4-122827101-G-A
• rs796052159
• ENST00000264498.9:c.326G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4 BP6

The ENST00000264498.9(FGF2):​c.326G>A​(p.Gly109Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000925 in 1,081,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 9.2e-7 (0 hom.)
• Consequence: FGF2 ENST00000264498.9 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.105
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36319542).
• BP6: Variant 4-122827101-G-A is Benign according to our data. Variant chr4-122827101-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 207863.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF2	NM_001361665.2	c.-74G>A		5_prime_UTR_variant	Exon 1 of 3	ENST00000644866.2	NP_001348594.1
FGF2	NM_002006.6	c.326G>A	p.Gly109Asp	missense_variant	Exon 1 of 3		NP_001997.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF2	ENST00000264498.9	c.326G>A	p.Gly109Asp	missense_variant	Exon 1 of 3	1		ENSP00000264498.4
FGF2	ENST00000644866.2	c.-74G>A		5_prime_UTR_variant	Exon 1 of 3		NM_001361665.2	ENSP00000494222.1
FGF2	ENST00000608478.1	c.-74G>A		5_prime_UTR_variant	Exon 1 of 3	1		ENSP00000477134.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 9.25e-7 AC: 1 AN: 1081124 Hom.: 0 Cov.: 31 AF XY: 0.00000195 AC XY: 1 AN XY: 514006

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 21724

American (AMR) AF: 0.00 AC: 0 AN: 7326

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13256

East Asian (EAS) AF: 0.00 AC: 0 AN: 23916

South Asian (SAS) AF: 0.0000385 AC: 1 AN: 25994

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22812

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2822

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 920580

Other (OTH) AF: 0.00 AC: 0 AN: 42694

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Long QT syndrome Benign:1

-

Medical Research Institute, Tokyo Medical and Dental University

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.080	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	.;T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.43	T;T
M_CAP	Pathogenic	0.71	D
MetaRNN	Benign	0.36	T;T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	0.34	.;N
PhyloP100		-0.10
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.37	N;.
REVEL	Uncertain	0.36
Sift	Uncertain	0.0060	D;.
Sift4G	Uncertain	0.0090	D;D
Polyphen		0.99	.;D
MutPred		0.32		Gain of solvent accessibility (P = 0.0281);Gain of solvent accessibility (P = 0.0281);
MVP		0.80
ClinPred		0.83	D
GERP RS		2.1
PromoterAI		-0.051	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.23
gMVP		0.13
Mutation Taster		=289/11	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: rs796052159; hg19: chr4-123748256;