rs10452197

Variant names:

• chr4-122889173-T-C
• rs10452197
• NM_001361665.2:c.283-3038T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001361665.2(FGF2):​c.283-3038T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,154 control chromosomes in the GnomAD database, including 1,139 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 0.12 (1139 hom., cov: 32)
• Consequence: FGF2 NM_001361665.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400
• Publications: 11 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]

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

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.283-3038T>C		intron	N/A	NP_001348594.1	D9ZGF5
	FGF2	NM_002006.6		c.682-3038T>C		intron	N/A	NP_001997.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF2	ENST00000644866.2	MANE Select	c.283-3038T>C		intron	N/A	ENSP00000494222.1	P09038-2
	FGF2	ENST00000264498.9	TSL:1	c.682-3038T>C		intron	N/A	ENSP00000264498.4	P09038-4
	FGF2	ENST00000608478.1	TSL:1	c.283-3038T>C		intron	N/A	ENSP00000477134.1	P09038-2

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17826 AN: 152036 Hom.: 1138 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0830

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0846

Gnomad FIN AF: 0.0993

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.125

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.117 AC: 17838 AN: 152154 Hom.: 1139 Cov.: 32 AF XY: 0.113 AC XY: 8410 AN XY: 74398

African (AFR) AF: 0.117 AC: 4857 AN: 41526

American (AMR) AF: 0.0829 AC: 1266 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 528 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.0845 AC: 407 AN: 4816

European-Finnish (FIN) AF: 0.0993 AC: 1051 AN: 10580

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9309 AN: 67988

Other (OTH) AF: 0.123 AC: 261 AN: 2114

Alfa AF: 0.133 Hom.: 1631

Bravo AF: 0.116

Asia WGS AF: 0.0410 AC: 142 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.3
DANN	Benign	0.91
PhyloP100		-0.0040
Mutation Taster		=100/0	polymorphism (auto)

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: rs10452197; hg19: chr4-123810328;