NM_006612.6(KIF1C):c.2591G>A (p.Arg864His) AND Spastic ataxia 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 18, 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:: RCV000809178.4

Allele description [Variation Report for NM_006612.6(KIF1C):c.2591G>A (p.Arg864His)]

NM_006612.6(KIF1C):c.2591G>A (p.Arg864His)

Gene:

KIF1C:kinesin family member 1C [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p13.2

Genomic location:

Preferred name:

NM_006612.6(KIF1C):c.2591G>A (p.Arg864His)

HGVS:

NC_000017.11:g.5022672G>A
NG_034137.1:g.29725G>A
NM_006612.6:c.2591G>AMANE SELECT
NP_006603.2:p.Arg864His
NC_000017.10:g.4925967G>A
NM_006612.5:c.2591G>A

Protein change:

R864H

Links:

dbSNP: rs146628704

NCBI 1000 Genomes Browser:

rs146628704

Molecular consequence:

NM_006612.6:c.2591G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Spastic ataxia 2
Synonyms:: Ataxia, spastic, 2, autosomal recessive
Identifiers:: MONDO: MONDO:0012651; MedGen: C1969796; Orphanet: 397946; OMIM: 611302

Recent activity

Clear Turn Off Turn On

APPL1 [Homo sapiens]
APPL1 [Homo sapiens]
gi|1352798264|gb|AVJ35780.1|

Protein

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000949320	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 18, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28832565, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000949320

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 18, 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

Massive sequencing of 70 genes reveals a myriad of missing genes or mechanisms to be uncovered in hereditary spastic paraplegias.

Morais S, Raymond L, Mairey M, Coutinho P, Brandão E, Ribeiro P, Loureiro JL, Sequeiros J, Brice A, Alonso I, Stevanin G.

Eur J Hum Genet. 2017 Nov;25(11):1217-1228. doi: 10.1038/ejhg.2017.124. Epub 2017 Aug 23.

PubMed [citation]

PMID:: 28832565
PMCID:: PMC5643959

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, SCV000949320.3

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

Description

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 864 of the KIF1C protein (p.Arg864His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with hereditary spastic paraplegia, but no second variant was identified (PMID: 28832565). ClinVar contains an entry for this variant (Variation ID: 424676). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.

#	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: Oct 20, 2024

ClinVar

Relating variation to medicine