NM_004984.4(KIF5A):c.827A>G (p.Tyr276Cys) AND Spastic paraplegia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 8, 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:: RCV000534416.5

Allele description [Variation Report for NM_004984.4(KIF5A):c.827A>G (p.Tyr276Cys)]

NM_004984.4(KIF5A):c.827A>G (p.Tyr276Cys)

Gene:

KIF5A:kinesin family member 5A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q13.3

Genomic location:

Preferred name:

NM_004984.4(KIF5A):c.827A>G (p.Tyr276Cys)

HGVS:

NC_000012.12:g.57569263A>G
NG_008155.1:g.24200A>G
NM_001354705.2:c.560A>G
NM_004984.4:c.827A>GMANE SELECT
NP_001341634.1:p.Tyr187Cys
NP_004975.2:p.Tyr276Cys
NC_000012.11:g.57963046A>G
NM_004984.2:c.827A>G
Q12840:p.Tyr276Cys

Protein change:

Y187C; TYR276CYS

Links:

UniProtKB: Q12840#VAR_033108; OMIM: 602821.0003; dbSNP: rs121434443

NCBI 1000 Genomes Browser:

rs121434443

Molecular consequence:

NM_001354705.2:c.560A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_004984.4:c.827A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Recent activity

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Homo sapiens DDAH family member 2, ADMA-independent (DDAH2), transcript variant ...
Homo sapiens DDAH family member 2, ADMA-independent (DDAH2), transcript variant 2, mRNA
gi|1676439696|ref|NM_013974.3|

Nucleotide
ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit, partial (chloropl...
ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit, partial (chloroplast) [Terminalia bellirica]
gi|2173475797|gb|UIE34992.1|

Protein
maturase K, partial (chloroplast) [Terminalia bellirica]
maturase K, partial (chloroplast) [Terminalia bellirica]
gi|2289199455|gb|UVI62084.1|

Protein
Megastigmus suspectus isolate Msus.ESP cytochrome b (cytb) gene, partial cds; mi...
Megastigmus suspectus isolate Msus.ESP cytochrome b (cytb) gene, partial cds; mitochondrial
gi|60250688|gb|AY898688.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000629426	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 8, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 16489470, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000629426

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 8, 2022)

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
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutation in KIF5A can also cause adult-onset hereditary spastic paraplegia.

Blair MA, Ma S, Hedera P.

Neurogenetics. 2006 Mar;7(1):47-50. Epub 2006 Feb 18.

PubMed [citation]

PMID:: 16489470

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

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000629426.4

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

Description

ClinVar contains an entry for this variant (Variation ID: 6808). For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt KIF5A protein function. This missense change has been observed in individual(s) with hereditary spastic paraplegia (PMID: 16489470; Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 276 of the KIF5A protein (p.Tyr276Cys).

#	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: Sep 29, 2024

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