6-1390041-CCCGCCGCCG-C

Position:

• chr6-1390041-CCCGCCGCCG-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6 BS2

The NM_001452.2(FOXF2):​c.115_123del​(p.Ala39_Ala41del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000794 in 1,354,610 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0017 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00069 (1 hom.)
• Consequence: FOXF2 NM_001452.2 inframe_deletion
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 3.31

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP6: Variant 6-1390041-CCCGCCGCCG-C is Benign according to our data. Variant chr6-1390041-CCCGCCGCCG-C is described in ClinVar as [Likely_benign]. Clinvar id is 3041547.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 245 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXF2	NM_001452.2	c.115_123del	p.Ala39_Ala41del	inframe_deletion	1/2	ENST00000645481.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXF2	ENST00000645481.2	c.115_123del	p.Ala39_Ala41del	inframe_deletion	1/2		NM_001452.2	P1

Frequencies

GnomAD3 genomes AF: 0.00169 AC: 245 AN: 145194 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00424

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00136

Gnomad ASJ AF: 0.00206

Gnomad EAS AF: 0.00103

Gnomad SAS AF: 0.000213

Gnomad FIN AF: 0.000468

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000502

Gnomad OTH AF: 0.00249

GnomAD3 exomes AF: 0.00167 AC: 57 AN: 34036 Hom.: 1 AF XY: 0.00147 AC XY: 29 AN XY: 19760

Gnomad AFR exome AF: 0.00962

Gnomad AMR exome AF: 0.00168

Gnomad ASJ exome AF: 0.00138

Gnomad EAS exome AF: 0.00221

Gnomad SAS exome AF: 0.00109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00187

Gnomad OTH exome AF: 0.00523

GnomAD4 exome AF: 0.000686 AC: 830 AN: 1209318 Hom.: 1 AF XY: 0.000677 AC XY: 402 AN XY: 593744

Gnomad4 AFR exome AF: 0.00439

Gnomad4 AMR exome AF: 0.00167

Gnomad4 ASJ exome AF: 0.000778

Gnomad4 EAS exome AF: 0.000347

Gnomad4 SAS exome AF: 0.000798

Gnomad4 FIN exome AF: 0.0000355

Gnomad4 NFE exome AF: 0.000570

Gnomad4 OTH exome AF: 0.000954

GnomAD4 genome AF: 0.00169 AC: 245 AN: 145292 Hom.: 1 Cov.: 31 AF XY: 0.00160 AC XY: 113 AN XY: 70768

Gnomad4 AFR AF: 0.00423

Gnomad4 AMR AF: 0.00136

Gnomad4 ASJ AF: 0.00206

Gnomad4 EAS AF: 0.00103

Gnomad4 SAS AF: 0.000213

Gnomad4 FIN AF: 0.000468

Gnomad4 NFE AF: 0.000502

Gnomad4 OTH AF: 0.00247

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

FOXF2-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 09, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs747033801; hg19: chr6-1390276;