chr6-1390850-G-GGGC

Variant names:

• chr6-1390850-G-GGGC
• rs58230522
• NM_001452.2:c.917_919dupGCG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001452.2(FOXF2):​c.917_919dupGCG​(p.Gly306dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 1,417,052 control chromosomes in the GnomAD database, including 195,064 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.57 (25117 hom., cov: 0)
  • Exomes 𝑓: 0.51 (169947 hom.)
• Consequence: FOXF2 NM_001452.2 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820

Genes affected

FOXF2 (HGNC:3810): (forkhead box F2) FOXF2 encodes forkhead box F2, one of many human homologues of the Drosophila melanogaster transcription factor forkhead. FOXF2 is expressed in lung and placenta, and has been shown to transcriptionally activate several lung-specific genes. [provided by RefSeq, Jul 2008]

FOXF2-DT (HGNC:50662): (FOXF2 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXF2	NM_001452.2	c.917_919dupGCG	p.Gly306dup	disruptive_inframe_insertion	Exon 1 of 2	ENST00000645481.2	NP_001443.1
FOXF2-DT	NR_189294.1	n.68+139_68+141dupGCC		intron_variant	Intron 1 of 2
FOXF2-DT	NR_189295.1	n.68+139_68+141dupGCC		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXF2	ENST00000645481.2	c.917_919dupGCG	p.Gly306dup	disruptive_inframe_insertion	Exon 1 of 2		NM_001452.2	ENSP00000496415.1

Frequencies

GnomAD3 genomes AF: 0.567 AC: 85816 AN: 151302 Hom.: 25110 Cov.: 0

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.926

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.593

GnomAD2 exomes AF: 0.499 AC: 18078 AN: 36238 AF XY: 0.502

Gnomad AFR exome AF: 0.599

Gnomad AMR exome AF: 0.466

Gnomad ASJ exome AF: 0.500

Gnomad EAS exome AF: 0.888

Gnomad FIN exome AF: 0.385

Gnomad NFE exome AF: 0.425

Gnomad OTH exome AF: 0.488

GnomAD4 exome AF: 0.511 AC: 647060 AN: 1265652 Hom.: 169947 Cov.: 36 AF XY: 0.516 AC XY: 319105 AN XY: 617968

Gnomad4 AFR exome AF: 0.668 AC: 16732 AN: 25040

Gnomad4 AMR exome AF: 0.517 AC: 9586 AN: 18548

Gnomad4 ASJ exome AF: 0.576 AC: 11035 AN: 19142

Gnomad4 EAS exome AF: 0.936 AC: 27339 AN: 29210

Gnomad4 SAS exome AF: 0.706 AC: 41077 AN: 58156

Gnomad4 FIN exome AF: 0.440 AC: 13868 AN: 31528

Gnomad4 NFE exome AF: 0.482 AC: 495763 AN: 1027746

Gnomad4 Remaining exome AF: 0.555 AC: 29098 AN: 52454

GnomAD4 genome AF: 0.567 AC: 85868 AN: 151400 Hom.: 25117 Cov.: 0 AF XY: 0.568 AC XY: 42010 AN XY: 74010

Gnomad4 AFR AF: 0.654 AC: 0.65355 AN: 0.65355

Gnomad4 AMR AF: 0.541 AC: 0.541322 AN: 0.541322

Gnomad4 ASJ AF: 0.598 AC: 0.597977 AN: 0.597977

Gnomad4 EAS AF: 0.926 AC: 0.926349 AN: 0.926349

Gnomad4 SAS AF: 0.745 AC: 0.74511 AN: 0.74511

Gnomad4 FIN AF: 0.437 AC: 0.437049 AN: 0.437049

Gnomad4 NFE AF: 0.498 AC: 0.49808 AN: 0.49808

Gnomad4 OTH AF: 0.598 AC: 0.598197 AN: 0.598197

Alfa AF: 0.332 Hom.: 591

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mutation Taster		=87/13	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs58230522; hg19: chr6-1391085; COSMIC: COSV52525393; COSMIC: COSV52525393;