NM_001451.3(FOXF1):c.57_60del (p.Gly20fs) AND Alveolar capillary dysplasia with pulmonary venous misalignment

Germline classification:: Pathogenic (1 submission)
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001250411.2

Allele description [Variation Report for NM_001451.3(FOXF1):c.57_60del (p.Gly20fs)]

NM_001451.3(FOXF1):c.57_60del (p.Gly20fs)

Genes:

FENDRR:FOXF1 adjacent non-coding developmental regulatory RNA [Gene - OMIM - HGNC]
FOXF1:forkhead box F1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

16q24.1

Genomic location:

Preferred name:

NM_001451.3(FOXF1):c.57_60del (p.Gly20fs)

HGVS:

NC_000016.10:g.86510626_86510629del
NG_016273.1:g.5100_5103del
NM_001451.3:c.57_60delMANE SELECT
NP_001442.2:p.Gly20fs
NC_000016.9:g.86544232_86544235del
NM_001451.2:c.57_60del
p.(Gly20Glufs*49)

Protein change:

G20fs

Links:

dbSNP: rs1969545531

NCBI 1000 Genomes Browser:

rs1969545531

Molecular consequence:

NM_001451.3:c.57_60del - frameshift variant - [Sequence Ontology: SO:0001589]

Functional consequence:

functionally_abnormal [Sequence Ontology: SO:0002218]

Observations:

Condition(s)

Name:: Alveolar capillary dysplasia with pulmonary venous misalignment
Synonyms:: ALVEOLAR CAPILLARY DYSPLASIA WITH MISALIGNMENT OF PULMONARY VEINS AND OTHER CONGENITAL ANOMALIES; Alveolar capillary dysplasia with misalignment of pulmonary veins; Congenital alveolar capillary dysplasia
Identifiers:: MONDO: MONDO:0009934; MedGen: C2960310; Orphanet: 210122; OMIM: 265380

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001364063	Institute for Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	de novo	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001364063

Institute for Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

de novo

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	de novo	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Institute for Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin, SCV001364063.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1		1	not provided	not provided	clinical testing	PubMed (1)

Description

The patient was diagnosed with a deletion of four base pairs in the FOXF1 gene. The result could be confirmed by Sanger sequencing. The above sequence variant was not detectable in the parents. Therefore, the sequence variant probably originated de novo. FOXF1 (MIM* 601089) encodes for the transcription factor Forkhead-Box-F1 (FOXF1) Heterozygous mutations in FOXF1 are associated with the clinical picture of congenital alveolar capillary dysplasia (ACDMPV, MIM #265380). Newborns present with severe respiratory insufficiency with therapy-refractory persistent pulmonary hypertension due to an altered air-blood barrier in the alveoli. Histologically there is a drastic reduction of the capillaries. Sequence variant c.57_60del leads to a shift in the reading frame and thus very probably to premature termination of protein biosynthesis. The variant is not listed in the population database gnomAD. To our knowledge the sequence variant has not been described as the cause of alveolar capillary dysplasia. Similar functional loss mutations have already been described as causative (Szafranski et al. 2016; Bourque et al. 2019; HGMD). According to current knowledge, this is a pathogenic sequence variant (class V).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	de novo	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Jun 24, 2022

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