6-1389960-G-C

Variant names:

• chr6-1389960-G-C
• NM_001452.2:c.13G>C

Variant summary

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

The NM_001452.2(FOXF2):​c.13G>C​(p.Gly5Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000117 in 852,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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: 0.0000012 (0 hom.)
• Consequence: FOXF2 NM_001452.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.830

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=0.10487676).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXF2	NM_001452.2	c.13G>C	p.Gly5Arg	missense_variant	Exon 1 of 2	ENST00000645481.2	NP_001443.1
FOXF2-DT	NR_189293.1	n.458+122C>G		intron_variant	Intron 1 of 2
FOXF2-DT	NR_189294.1	n.69-734C>G		intron_variant	Intron 1 of 2
FOXF2-DT	NR_189295.1	n.68+1032C>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXF2	ENST00000645481.2	c.13G>C	p.Gly5Arg	missense_variant	Exon 1 of 2		NM_001452.2	ENSP00000496415.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000117 AC: 1 AN: 852758 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 398114

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: 0.00000129

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	0.25
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.035	T;T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.43	.;T
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	0.55	N;N
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.38	.;N
REVEL	Benign	0.18
Sift	Benign	0.043	.;D
Sift4G	Benign	0.21	.;T
Polyphen		0.093	B;B
Vest4		0.015
MutPred		0.14		Gain of methylation at G5 (P = 0.0348);Gain of methylation at G5 (P = 0.0348);
MVP		0.48
ClinPred		0.12	T
GERP RS		0.27
Varity_R		0.13
gMVP		0.55

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-1390195;