6-1390041-CCCGCCGCCGCCG-C

Position:

• chr6-1390041-CCCGCCGCCGCCG-C

Variant summary

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

The NM_001452.2(FOXF2):​c.112_123del​(p.Ala38_Ala41del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000935 in 1,354,762 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00086 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00094 (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-CCCGCCGCCGCCG-C is Benign according to our data. Variant chr6-1390041-CCCGCCGCCGCCG-C is described in ClinVar as [Likely_benign]. Clinvar id is 3047212.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 125 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXF2	NM_001452.2	c.112_123del	p.Ala38_Ala41del	inframe_deletion	1/2	ENST00000645481.2	NP_001443.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXF2	ENST00000645481.2	c.112_123del	p.Ala38_Ala41del	inframe_deletion	1/2		NM_001452.2	ENSP00000496415	P1

Frequencies

GnomAD3 genomes AF: 0.000861 AC: 125 AN: 145198 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000324

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000681

Gnomad ASJ AF: 0.000590

Gnomad EAS AF: 0.00103

Gnomad SAS AF: 0.000852

Gnomad FIN AF: 0.000819

Gnomad MID AF: 0.00338

Gnomad NFE AF: 0.00140

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00209 AC: 71 AN: 34036 Hom.: 1 AF XY: 0.00152 AC XY: 30 AN XY: 19760

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000915

Gnomad ASJ exome AF: 0.00381

Gnomad EAS exome AF: 0.00221

Gnomad SAS exome AF: 0.000136

Gnomad FIN exome AF: 0.00301

Gnomad NFE exome AF: 0.00342

Gnomad OTH exome AF: 0.00105

GnomAD4 exome AF: 0.000944 AC: 1142 AN: 1209466 Hom.: 1 AF XY: 0.000914 AC XY: 543 AN XY: 593834

Gnomad4 AFR exome AF: 0.000123

Gnomad4 AMR exome AF: 0.000278

Gnomad4 ASJ exome AF: 0.00197

Gnomad4 EAS exome AF: 0.000347

Gnomad4 SAS exome AF: 0.000374

Gnomad4 FIN exome AF: 0.00110

Gnomad4 NFE exome AF: 0.00102

Gnomad4 OTH exome AF: 0.000663

GnomAD4 genome AF: 0.000860 AC: 125 AN: 145296 Hom.: 0 Cov.: 31 AF XY: 0.000918 AC XY: 65 AN XY: 70768

Gnomad4 AFR AF: 0.000323

Gnomad4 AMR AF: 0.0000680

Gnomad4 ASJ AF: 0.000590

Gnomad4 EAS AF: 0.00103

Gnomad4 SAS AF: 0.000853

Gnomad4 FIN AF: 0.000819

Gnomad4 NFE AF: 0.00140

Gnomad4 OTH AF: 0.00

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

Sep 01, 2022

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;