NM_015915.5(ATL1):c.1505_1506del (p.Glu502fs) AND Hereditary spastic paraplegia 3A

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jun 2, 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:: RCV002013922.5

Allele description [Variation Report for NM_015915.5(ATL1):c.1505_1506del (p.Glu502fs)]

NM_015915.5(ATL1):c.1505_1506del (p.Glu502fs)

Gene:

ATL1:atlastin GTPase 1 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

14q22.1

Genomic location:

Preferred name:

NM_015915.5(ATL1):c.1505_1506del (p.Glu502fs)

HGVS:

NC_000014.9:g.50628414AG[1]
NG_009028.1:g.100333AG[1]
NM_001127713.1:c.1505_1506del
NM_015915.4:c.1505_1506delAG
NM_015915.5:c.1505_1506delMANE SELECT
NM_181598.4:c.1505_1506del
NP_001121185.1:p.Glu502fs
NP_056999.2:p.Glu502fs
NP_853629.2:p.Glu502fs
LRG_360t1:c.1505_1506del
LRG_360t2:c.1505_1506del
LRG_360:g.100333AG[1]
LRG_360p2:p.Glu502fs
NC_000014.8:g.51095131_51095132del
NC_000014.8:g.51095132AG[1]

Protein change:

E502fs

Links:

dbSNP: rs2140239392

NCBI 1000 Genomes Browser:

rs2140239392

Molecular consequence:

NM_001127713.1:c.1505_1506del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_015915.5:c.1505_1506del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_181598.4:c.1505_1506del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Hereditary spastic paraplegia 3A (SPG3A)
Synonyms:: SPASTIC PARAPLEGIA 3, AUTOSOMAL DOMINANT; FAMILIAL SPASTIC PARAPLEGIA, AUTOSOMAL DOMINANT, 1; SPG3; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008437; MedGen: C2931355; Orphanet: 100984; OMIM: 182600

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002299428	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 2, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23108492, 28492532
SCV004011947	Inherited Neuropathy Consortium Ii, University Of Miami	no assertion criteria provided	Uncertain significance (Jan 6, 2016)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002299428

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 2, 2023)

germline

clinical testing

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

SCV004011947

Inherited Neuropathy Consortium Ii, University Of Miami

no assertion criteria provided

Uncertain significance
(Jan 6, 2016)

germline

literature only

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	germline	yes	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

ATL1 and REEP1 mutations in hereditary and sporadic upper motor neuron syndromes.

de Bot ST, Veldink JH, Vermeer S, Mensenkamp AR, Brugman F, Scheffer H, van den Berg LH, Kremer HP, Kamsteeg EJ, van de Warrenburg BP.

J Neurol. 2013 Mar;260(3):869-75. doi: 10.1007/s00415-012-6723-z. Epub 2012 Oct 30.

PubMed [citation]

PMID:: 23108492

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002299428.3

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This premature translational stop signal has been observed in individual(s) with hereditary spastic paraplegia (PMID: 23108492). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu502Alafs*20) in the ATL1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 57 amino acid(s) of the ATL1 protein.

#	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

From Inherited Neuropathy Consortium Ii, University Of Miami, SCV004011947.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

#	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		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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