NM_001244008.2(KIF1A):c.760C>T (p.Arg254Trp) AND Intellectual disability, autosomal dominant 9

Clinical significance:Pathogenic (Last evaluated: Jun 15, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000995795.4

Allele description [Variation Report for NM_001244008.2(KIF1A):c.760C>T (p.Arg254Trp)]

NM_001244008.2(KIF1A):c.760C>T (p.Arg254Trp)

Gene:
KIF1A:kinesin family member 1A [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q37.3
Genomic location:
Preferred name:
NM_001244008.2(KIF1A):c.760C>T (p.Arg254Trp)
HGVS:
  • NC_000002.12:g.240783777G>A
  • NG_029724.1:g.41431C>T
  • NM_001244008.1:c.760C>T
  • NM_001244008.2:c.760C>TMANE SELECT
  • NM_001320705.2:c.760C>T
  • NM_001330289.2:c.760C>T
  • NM_001330290.2:c.760C>T
  • NM_001379631.1:c.760C>T
  • NM_001379632.1:c.760C>T
  • NM_001379633.1:c.760C>T
  • NM_001379634.1:c.760C>T
  • NM_001379635.1:c.760C>T
  • NM_001379636.1:c.760C>T
  • NM_001379637.1:c.760C>T
  • NM_001379638.1:c.760C>T
  • NM_001379639.1:c.760C>T
  • NM_001379640.1:c.760C>T
  • NM_001379641.1:c.760C>T
  • NM_001379642.1:c.760C>T
  • NM_001379645.1:c.760C>T
  • NM_001379646.1:c.760C>T
  • NM_001379648.1:c.760C>T
  • NM_001379649.1:c.760C>T
  • NM_001379650.1:c.760C>T
  • NM_001379651.1:c.760C>T
  • NM_001379653.1:c.760C>T
  • NM_004321.7:c.760C>T
  • NM_004321.8:c.760C>T
  • NP_001230937.1:p.Arg254Trp
  • NP_001230937.1:p.Arg254Trp
  • NP_001307634.1:p.Arg254Trp
  • NP_001317218.1:p.Arg254Trp
  • NP_001317219.1:p.Arg254Trp
  • NP_001366560.1:p.Arg254Trp
  • NP_001366561.1:p.Arg254Trp
  • NP_001366562.1:p.Arg254Trp
  • NP_001366563.1:p.Arg254Trp
  • NP_001366564.1:p.Arg254Trp
  • NP_001366565.1:p.Arg254Trp
  • NP_001366566.1:p.Arg254Trp
  • NP_001366567.1:p.Arg254Trp
  • NP_001366568.1:p.Arg254Trp
  • NP_001366569.1:p.Arg254Trp
  • NP_001366570.1:p.Arg254Trp
  • NP_001366571.1:p.Arg254Trp
  • NP_001366574.1:p.Arg254Trp
  • NP_001366575.1:p.Arg254Trp
  • NP_001366577.1:p.Arg254Trp
  • NP_001366578.1:p.Arg254Trp
  • NP_001366579.1:p.Arg254Trp
  • NP_001366580.1:p.Arg254Trp
  • NP_001366582.1:p.Arg254Trp
  • NP_004312.2:p.Arg254Trp
  • NP_004312.2:p.Arg254Trp
  • LRG_367t1:c.760C>T
  • LRG_367t2:c.760C>T
  • LRG_367:g.41431C>T
  • LRG_367p1:p.Arg254Trp
  • LRG_367p2:p.Arg254Trp
  • NC_000002.11:g.241723194G>A
  • NM_004321.5:c.760C>T
  • NM_004321.6:c.760C>T
  • NM_001224008.1:c.760C>T
Protein change:
R254W; ARG254TRP
Links:
OMIM: 601255.0012; dbSNP: rs879253888
NCBI 1000 Genomes Browser:
rs879253888
Molecular consequence:
  • NM_001244008.1:c.760C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001244008.2:c.760C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001320705.2:c.760C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330289.2:c.760C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330290.2:c.760C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379631.1:c.760C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379632.1:c.760C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379633.1:c.760C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379634.1:c.760C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379635.1:c.760C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379636.1:c.760C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379637.1:c.760C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379638.1:c.760C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379639.1:c.760C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379640.1:c.760C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379641.1:c.760C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379642.1:c.760C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379645.1:c.760C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379646.1:c.760C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379648.1:c.760C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379649.1:c.760C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379650.1:c.760C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379651.1:c.760C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379653.1:c.760C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004321.7:c.760C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004321.8:c.760C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Intellectual disability, autosomal dominant 9 (NESCAVS)
Synonyms:
Mental retardation, autosomal dominant 9; NESCAV SYNDROME; NEURODEGENERATION AND SPASTICITY WITH OR WITHOUT CEREBELLAR ATROPHY OR CORTICAL VISUAL IMPAIRMENT
Identifiers:
MONDO: MONDO:0013656; MedGen: C5393830; OMIM: 614255

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001150146Institute of Human Genetics, Klinikum rechts der Isarcriteria provided, single submitter
Pathogenic
(Jan 30, 2018)
de novoclinical testing

Citation Link,

SCV001244201OMIMno assertion criteria providedPathogenic
(Apr 16, 2020)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

SCV001426707SIB Swiss Institute of Bioinformaticscriteria provided, single submitter
Pathogenic
(Jun 15, 2020)
unknowncuration

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedde novoyes1not providednot provided1not providedclinical testing
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only
not providedunknownunknownnot providednot providednot providednot providednot providedcuration

Citations

PubMed

De novo KIF1A mutations cause intellectual deficit, cerebellar atrophy, lower limb spasticity and visual disturbance.

Ohba C, Haginoya K, Osaka H, Kubota K, Ishiyama A, Hiraide T, Komaki H, Sasaki M, Miyatake S, Nakashima M, Tsurusaki Y, Miyake N, Tanaka F, Saitsu H, Matsumoto N.

J Hum Genet. 2015 Dec;60(12):739-42. doi: 10.1038/jhg.2015.108. Epub 2015 Sep 10.

PubMed [citation]
PMID:
26354034

KIF1A-related disorders in children: A wide spectrum of central and peripheral nervous system involvement.

Nemani T, Steel D, Kaliakatsos M, DeVile C, Ververi A, Scott R, Getov S, Sudhakar S, Male A, Mankad K; Genomics England Research Consortium., Muntoni F, Reilly MM, Kurian MA, Carr L, Munot P.

J Peripher Nerv Syst. 2020 Jun;25(2):117-124. doi: 10.1111/jns.12368. Epub 2020 Mar 6.

PubMed [citation]
PMID:
32096284
See all PubMed Citations (3)

Details of each submission

From Institute of Human Genetics, Klinikum rechts der Isar, SCV001150146.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1de novoyes1bloodnot provided1not providednot providednot provided

From OMIM, SCV001244201.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In a 27-year-old woman (patient 2) with NESCAV syndrome (NESCAVS; 614255), Ohba et al. (2015) identified a de novo heterozygous c.760C-T transition (c.760C-T, NM_001224008.1) in the KIF1A gene, resulting in an arg254-to-trp (R254W) substitution at a conserved residue in the motor domain. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the dbSNP (build 138), Exome Sequencing Project, 1000 Genomes Project, or ExAC databases, or in an in-house database of 575 control exomes. Functional studies of the variant and studies of patient cells were not performed.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

From SIB Swiss Institute of Bioinformatics, SCV001426707.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (3)

Description

This variant is interpreted as pathogenic for NESCAV syndrome, autosomal dominant. The following ACMG Tag(s) were applied: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium (PM2); De novo (paternity and maternity confirmed) (PS2); Multiple lines of computational evidence support a deleterious effect on the gene or gene product (PP3); Missense variant in a gene that has a low rate of benign missense variation and in which missense variants are a common mechanism of disease (PP2); Located in a mutational hot spot and/or critical and well-established functional domain (e.g., active site of an enzyme) without benign variation (PM1 downgraded to supporting); Prevalence in affected individuals statistically increased over controls (PS4 downgraded to supporting).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 16, 2021

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