4-122826956-G-C

Variant names:

• chr4-122826956-G-C
• ENST00000264498.9:c.181G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002006.6(FGF2):​c.181G>C​(p.Gly61Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000025 in 1,197,628 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000025 (0 hom.)
• Consequence: FGF2 NM_002006.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0530

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29623485).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF2	NM_001361665.2	c.-219G>C		5_prime_UTR_variant	Exon 1 of 3	ENST00000644866.2	NP_001348594.1
FGF2	NM_002006.6	c.181G>C	p.Gly61Arg	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.181G>C	p.Gly61Arg	missense_variant	Exon 1 of 3	1		ENSP00000264498.4
FGF2	ENST00000644866	c.-219G>C		5_prime_UTR_variant	Exon 1 of 3		NM_001361665.2	ENSP00000494222.1
FGF2	ENST00000608478	c.-219G>C		5_prime_UTR_variant	Exon 1 of 3	1		ENSP00000477134.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000250 AC: 3 AN: 1197628 Hom.: 0 Cov.: 32 AF XY: 0.00000344 AC XY: 2 AN XY: 580656

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000307

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	9.5
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	.;T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.0084	N
LIST_S2	Benign	0.46	T;T
M_CAP	Pathogenic	0.66	D
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	0.0	.;N
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	0.13	N;.
REVEL	Benign	0.28
Sift	Pathogenic	0.0	D;.
Sift4G	Uncertain	0.011	D;D
Polyphen		0.99	.;D
MutPred		0.29		Gain of methylation at G61 (P = 0.0151);Gain of methylation at G61 (P = 0.0151);
MVP		0.85
ClinPred		0.37	T
GERP RS		2.0
Varity_R		0.071
gMVP		0.042

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-123748111;