Genetic Variant FOXF2:p.Ala38_Ala41dup (chr6-1390041-C-CCCGCCGCCGCCG) – 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.112_123dupGCCGCCGCCGCC(p.Ala38_Ala41dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000413 in 145,300 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P42P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000041 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000028 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FOXF2
NM_001452.2 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.89

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BS2

High AC in GnomAd4 at 6 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.112_123dupGCCGCCGCCGCC	p.Ala38_Ala41dup	conservative_inframe_insertion	Exon 1 of 2	NP_001443.1	Q12947
FOXF2-DT	NR_189293.1		n.458+29_458+40dupCGGCGGCGGCGG		intron	N/A
FOXF2-DT	NR_189294.1		n.69-827_69-816dupCGGCGGCGGCGG		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FOXF2	ENST00000645481.2	MANE Select	c.112_123dupGCCGCCGCCGCC	p.Ala38_Ala41dup	conservative_inframe_insertion	Exon 1 of 2	ENSP00000496415.1	Q12947
LINC01394	ENST00000721686.1		n.89+939_89+950dupCGGCGGCGGCGG		intron	N/A
LINC01394	ENST00000721687.1		n.69-827_69-816dupCGGCGGCGGCGG		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000413

AC:

AN:

145202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000136

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000413

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000304

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000281

AC:

AN:

1209594

Hom.:

Cov.:

AF XY:

0.0000320

AC XY:

AN XY:

593910

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24358

American (AMR)

AF:

0.00

AC:

AN:

21586

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19290

East Asian (EAS)

AF:

0.0000868

AC:

AN:

23044

South Asian (SAS)

AF:

0.00

AC:

AN:

58922

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28178

Middle Eastern (MID)

AF:

0.000292

AC:

AN:

3424

European-Non Finnish (NFE)

AF:

0.0000305

AC:

AN:

982540

Other (OTH)

AF:

0.0000207

AC:

AN:

48252

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.410

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:

0.0000413

AC:

AN:

145300

Hom.:

Cov.:

AF XY:

0.0000424

AC XY:

AN XY:

70770

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40206

American (AMR)

AF:

0.000136

AC:

AN:

14708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3392

East Asian (EAS)

AF:

0.000414

AC:

AN:

4832

South Asian (SAS)

AF:

0.00

AC:

AN:

4692

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8546

Middle Eastern (MID)

AF:

0.00

AC:

AN:

276

European-Non Finnish (NFE)

AF:

0.0000304

AC:

AN:

65732

Other (OTH)

AF:

0.00

AC:

AN:

2026

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.9

Mutation Taster

=85/15

polymorphism

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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6-1390041-CCCGCCGCCGCCGCCGCCGCCG-CCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCG

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