Genetic Variant FOXF2:p.Gly305_Gly306dup (chr6-1390850-G-GGGCGGC) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001452.2(FOXF2):c.914_919dupGCGGCG(p.Gly305_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 0.0000148 in 1,418,232 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

FOXF2
NM_001452.2 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0820

Publications

2 publications found

Variant links:

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 links:

LINC01394 (HGNC:50670): (long intergenic non-protein coding RNA 1394)

LINC01394 links:

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

FOXF2-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 17 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001452.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FOXF2	NM_001452.2	MANE Select	c.914_919dupGCGGCG	p.Gly305_Gly306dup	disruptive_inframe_insertion	Exon 1 of 2	NP_001443.1	Q12947
FOXF2-DT	NR_189294.1		n.68+136_68+141dupGCCGCC		intron	N/A
FOXF2-DT	NR_189295.1		n.68+136_68+141dupGCCGCC		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FOXF2	ENST00000645481.2	MANE Select	c.914_919dupGCGGCG	p.Gly305_Gly306dup	disruptive_inframe_insertion	Exon 1 of 2	ENSP00000496415.1	Q12947
LINC01394	ENST00000721686.1		n.89+136_89+141dupGCCGCC		intron	N/A
LINC01394	ENST00000721687.1		n.68+136_68+141dupGCCGCC		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000264

AC:

AN:

151336

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000729

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.0000276

AC:

AN:

36238

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000653

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000134

AC:

AN:

1266896

Hom.:

Cov.:

AF XY:

0.0000162

AC XY:

AN XY:

618670

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25056

American (AMR)

AF:

0.00

AC:

AN:

18662

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19176

East Asian (EAS)

AF:

0.0000685

AC:

AN:

29218

South Asian (SAS)

AF:

0.0000514

AC:

AN:

58362

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31566

Middle Eastern (MID)

AF:

0.000261

AC:

AN:

3832

European-Non Finnish (NFE)

AF:

0.00000778

AC:

AN:

1028530

Other (OTH)

AF:

0.0000571

AC:

AN:

52494

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000264

AC:

AN:

151336

Hom.:

Cov.:

AF XY:

0.0000541

AC XY:

AN XY:

73922

show subpopulations

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

African (AFR)

AF:

0.0000729

AC:

AN:

41172

American (AMR)

AF:

0.00

AC:

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5094

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10536

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67734

Other (OTH)

AF:

0.000479

AC:

AN:

2086

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000000286219), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.388

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

591

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.082

Mutation Taster

=87/13

polymorphism

(source)

Splicing

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

Publications

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6-1390850-GGGCGGC-GGGCGGCGGCGGC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over