NM_017791.3(FLVCR2):c.191del (p.Leu64fs) AND Fowler syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Apr 20, 2023
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:: RCV004720588.1

Allele description [Variation Report for NM_017791.3(FLVCR2):c.191del (p.Leu64fs)]

NM_017791.3(FLVCR2):c.191del (p.Leu64fs)

Genes:

FLVCR2:FLVCR choline and putative heme transporter 2 [Gene - OMIM - HGNC]
FLVCR2-AS1:FLVCR2 antisense RNA 1 [Gene - HGNC]

Variant type:

Deletion

Cytogenetic location:

14q24.3

Genomic location:

Preferred name:

NM_017791.3(FLVCR2):c.191del (p.Leu64fs)

HGVS:

NC_000014.9:g.75579163del
NG_027694.1:g.5567del
NM_017791.3:c.191delMANE SELECT
NP_060261.2:p.Leu64fs
NC_000014.8:g.76045506del
NR_110552.1:n.427del

Protein change:

L64fs

Molecular consequence:

NM_017791.3:c.191del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_110552.1:n.427del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Name:: Fowler syndrome
Synonyms:: ENCEPHALOCLASTIC PROLIFERATIVE VASCULOPATHY; HYDRANENCEPHALY, FOWLER TYPE; HYDROCEPHALY/HYDRANENCEPHALY DUE TO CEREBRAL VASCULOPATHY; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009168; MedGen: C1856972; OMIM: 225790

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005328370	Faculty of Engineering and Natural Sciences, Biruni University	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 20, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25677735, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005328370

Faculty of Engineering and Natural Sciences, Biruni University

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Apr 20, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
West Asian	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in FLVCR2 associated with Fowler syndrome and survival beyond infancy.

Kvarnung M, Taylan F, Nilsson D, Albåge M, Nordenskjöld M, Anderlid BM, Nordgren A, Syk Lundberg E.

Clin Genet. 2016 Jan;89(1):99-103. doi: 10.1111/cge.12565. Epub 2015 Mar 4.

PubMed [citation]

PMID:: 25677735

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 Faculty of Engineering and Natural Sciences, Biruni University, SCV005328370.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	West Asian	1	not provided	not provided	clinical testing	PubMed (2)

Description

The NM_017791.3 c.191del, is a frameshift variant in FLVCR2 which is predicted to result in a premature stop codon at position 78, and likely results in an absent or disrupted protein product (PVS1). It was absent from large population studies(gnomAD)(PM2). The phenotypic features observed in the proband, including hydrocephalus and epilepsy attacks, are consistent with Fowler Syndrome, which has previously been associated with an autosomal recessive inheritance pattern in the FLVCR2 gene (PMID: 25677735). In the same proband, c.1021-7T>G change in the same gene was also detected. It is thought that these two variants together cause Fowler Syndrome by forming compound heterozygote.

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

Last Updated: Oct 8, 2024

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