chr6-1389999-C-G

Variant names:

• chr6-1389999-C-G
• rs927643069
• NM_001452.2:c.52C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001452.2(FOXF2):​c.52C>G​(p.Pro18Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FOXF2 NM_001452.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.20

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16689366).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXF2	NM_001452.2	c.52C>G	p.Pro18Ala	missense_variant	Exon 1 of 2	ENST00000645481.2	NP_001443.1
FOXF2-DT	NR_189293.1	n.458+83G>C		intron_variant	Intron 1 of 2
FOXF2-DT	NR_189294.1	n.69-773G>C		intron_variant	Intron 1 of 2
FOXF2-DT	NR_189295.1	n.68+993G>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXF2	ENST00000645481.2	c.52C>G	p.Pro18Ala	missense_variant	Exon 1 of 2		NM_001452.2	ENSP00000496415.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 938070 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 447230

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	21
DANN	Benign	0.90
DEOGEN2	Benign	0.11	T;T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.43	.;T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.69	N;N
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-1.1	.;N
REVEL	Benign	0.25
Sift	Benign	0.22	.;T
Sift4G	Pathogenic	0.0	.;D
Polyphen		0.056	B;B
Vest4		0.066
MutPred		0.18		Gain of helix (P = 0.0143);Gain of helix (P = 0.0143);
MVP		0.77
ClinPred		0.19	T
GERP RS		2.9
Varity_R		0.12
gMVP		0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs927643069; hg19: chr6-1390234;