NM_014946.4(SPAST):c.185dup (p.Leu63fs) AND Hereditary spastic paraplegia 4

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Sep 1, 2022
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:: RCV002283645.1

Allele description [Variation Report for NM_014946.4(SPAST):c.185dup (p.Leu63fs)]

NM_014946.4(SPAST):c.185dup (p.Leu63fs)

Gene:

SPAST:spastin [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

2p22.3

Genomic location:

Preferred name:

NM_014946.4(SPAST):c.185dup (p.Leu63fs)

HGVS:

NC_000002.12:g.32064016dup
NG_008730.1:g.5406dup
NM_001363823.2:c.185dup
NM_001363875.2:c.185dup
NM_001377959.1:c.185dup
NM_014946.4:c.185dupMANE SELECT
NM_199436.2:c.185dup
NP_001350752.1:p.Leu63fs
NP_001350804.1:p.Leu63fs
NP_001364888.1:p.Leu63fs
NP_055761.2:p.Leu63Alafs
NP_055761.2:p.Leu63fs
NP_955468.1:p.Leu63fs
LRG_714t1:c.185dup
LRG_714:g.5406dup
LRG_714p1:p.Leu63Alafs
NC_000002.11:g.32289085dup
NM_014946.3:c.185dup

Protein change:

L63fs

Molecular consequence:

NM_001363823.2:c.185dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001363875.2:c.185dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001377959.1:c.185dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_014946.4:c.185dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_199436.2:c.185dup - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: Hereditary spastic paraplegia 4
Synonyms:: Spastic paraplegia 4, autosomal dominant; Familial spastic paraplegia autosomal dominant 2
Identifiers:: MONDO: MONDO:0008438; MedGen: C1866855; Orphanet: 100985; OMIM: 182601

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breast cancer type 1 susceptibility protein isoform 94 [Homo sapiens]
breast cancer type 1 susceptibility protein isoform 94 [Homo sapiens]
gi|2255446638|ref|NP_001395327.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002572600	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Sep 1, 2022)	germline	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

SCV002572600

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Sep 1, 2022)

germline

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	germline	yes	1	not provided	not provided	1	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 3billion, SCV002572600.1

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

Description

The variant is not observed in the gnomAD v2.1.1 dataset. Frameshift variant is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline.

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

Last Updated: Sep 24, 2022

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