NM_024306.5(FA2H):c.21del (p.Ala8fs) AND Spastic paraplegia

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 12, 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:: RCV001387014.6

Allele description

NM_024306.5(FA2H):c.21del (p.Ala8fs)

Genes:

LOC130059394:ATAC-STARR-seq lymphoblastoid silent region 7701 [Gene]
FA2H:fatty acid 2-hydroxylase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

16q23.1

Genomic location:

Preferred name:

NM_024306.5(FA2H):c.21del (p.Ala8fs)

HGVS:

NC_000016.10:g.74774740del
NG_017070.1:g.5097del
NM_024306.5:c.21delMANE SELECT
NP_077282.3:p.Ala8fs
NC_000016.9:g.74808633del
NC_000016.9:g.74808638del

Protein change:

A8fs

Links:

dbSNP: rs1962978296

NCBI 1000 Genomes Browser:

rs1962978296

Molecular consequence:

NM_024306.5:c.21del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Spastic paraplegia
Identifiers:: MedGen: C0037772; Human Phenotype Ontology: HP:0001258

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001587496	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 12, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 20853438, 25496456, 25732363, 26344562, 27165006, 31135052, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001587496

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 12, 2023)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Defective FA2H leads to a novel form of neurodegeneration with brain iron accumulation (NBIA).

Kruer MC, Paisán-Ruiz C, Boddaert N, Yoon MY, Hama H, Gregory A, Malandrini A, Woltjer RL, Munnich A, Gobin S, Polster BJ, Palmeri S, Edvardson S, Hardy J, Houlden H, Hayflick SJ.

Ann Neurol. 2010 Nov;68(5):611-8. doi: 10.1002/ana.22122.

PubMed [citation]

PMID:: 20853438
PMCID:: PMC6059612

Mutations in FA2H in three Arab families with a clinical spectrum of neurodegeneration and hereditary spastic paraparesis.

Zaki MS, Selim L, Mansour L, Mahmoud IG, Fenstermaker AG, Gabriel SB, Gleeson JG.

Clin Genet. 2015 Jul;88(1):95-7. doi: 10.1111/cge.12516. Epub 2014 Dec 11. No abstract available.

PubMed [citation]

PMID:: 25496456

See all PubMed Citations (7)

Details of each submission

From Invitae, SCV001587496.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This sequence change creates a premature translational stop signal (p.Ala8Profs*91) in the FA2H gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FA2H are known to be pathogenic (PMID: 20853438, 25496456, 25732363, 26344562). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with hereditary spastic paraplegia (PMID: 27165006, 31135052). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1073882). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Feb 20, 2024

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