4-122827461-C-T

Variant names:

• chr4-122827461-C-T
• rs2922979
• NM_001361665.2:c.178+109C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001361665.2(FGF2):​c.178+109C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000884 in 1,130,834 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 8.8e-7 (0 hom.)
• Consequence: FGF2 NM_001361665.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.141
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF2	NM_001361665.2	MANE Select	c.178+109C>T		intron	N/A	NP_001348594.1
	FGF2	NM_002006.6		c.577+109C>T		intron	N/A	NP_001997.5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF2	ENST00000644866.2	MANE Select	c.178+109C>T		intron	N/A	ENSP00000494222.1
	FGF2	ENST00000264498.9	TSL:1	c.577+109C>T		intron	N/A	ENSP00000264498.4
	FGF2	ENST00000608478.1	TSL:1	c.178+109C>T		intron	N/A	ENSP00000477134.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 8.84e-7 AC: 1 AN: 1130834 Hom.: 0 AF XY: 0.00000175 AC XY: 1 AN XY: 570682

⚠️ 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: 26410

American (AMR) AF: 0.00 AC: 0 AN: 37936

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23442

East Asian (EAS) AF: 0.00 AC: 0 AN: 35346

South Asian (SAS) AF: 0.00 AC: 0 AN: 75168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43110

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5134

European-Non Finnish (NFE) AF: 0.00000120 AC: 1 AN: 834914

Other (OTH) AF: 0.00 AC: 0 AN: 49374

⚠️ 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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.5
DANN	Benign	0.96
PhyloP100		0.14

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: rs2922979; hg19: chr4-123748616;