NM_001244008.2(KIF1A):c.920G>A (p.Arg307Gln) AND Intellectual disability, autosomal dominant 9

Clinical significance:Pathogenic/Likely 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:
RCV000496175.3

Allele description [Variation Report for NM_001244008.2(KIF1A):c.920G>A (p.Arg307Gln)]

NM_001244008.2(KIF1A):c.920G>A (p.Arg307Gln)

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.920G>A (p.Arg307Gln)
HGVS:
  • NC_000002.12:g.240775889C>T
  • NG_029724.1:g.49319G>A
  • NM_001244008.2:c.920G>AMANE SELECT
  • NM_001320705.2:c.920G>A
  • NM_001330289.2:c.920G>A
  • NM_001330290.2:c.920G>A
  • NM_001379631.1:c.920G>A
  • NM_001379632.1:c.920G>A
  • NM_001379633.1:c.920G>A
  • NM_001379634.1:c.920G>A
  • NM_001379635.1:c.920G>A
  • NM_001379636.1:c.920G>A
  • NM_001379637.1:c.920G>A
  • NM_001379638.1:c.920G>A
  • NM_001379639.1:c.920G>A
  • NM_001379640.1:c.920G>A
  • NM_001379641.1:c.920G>A
  • NM_001379642.1:c.920G>A
  • NM_001379645.1:c.920G>A
  • NM_001379646.1:c.920G>A
  • NM_001379648.1:c.920G>A
  • NM_001379649.1:c.920G>A
  • NM_001379650.1:c.920G>A
  • NM_001379651.1:c.920G>A
  • NM_001379653.1:c.920G>A
  • NM_004321.8:c.920G>A
  • NP_001230937.1:p.Arg307Gln
  • NP_001230937.1:p.Arg307Gln
  • NP_001307634.1:p.Arg307Gln
  • NP_001317218.1:p.Arg307Gln
  • NP_001317219.1:p.Arg307Gln
  • NP_001366560.1:p.Arg307Gln
  • NP_001366561.1:p.Arg307Gln
  • NP_001366562.1:p.Arg307Gln
  • NP_001366563.1:p.Arg307Gln
  • NP_001366564.1:p.Arg307Gln
  • NP_001366565.1:p.Arg307Gln
  • NP_001366566.1:p.Arg307Gln
  • NP_001366567.1:p.Arg307Gln
  • NP_001366568.1:p.Arg307Gln
  • NP_001366569.1:p.Arg307Gln
  • NP_001366570.1:p.Arg307Gln
  • NP_001366571.1:p.Arg307Gln
  • NP_001366574.1:p.Arg307Gln
  • NP_001366575.1:p.Arg307Gln
  • NP_001366577.1:p.Arg307Gln
  • NP_001366578.1:p.Arg307Gln
  • NP_001366579.1:p.Arg307Gln
  • NP_001366580.1:p.Arg307Gln
  • NP_001366582.1:p.Arg307Gln
  • NP_004312.2:p.Arg307Gln
  • NP_004312.2:p.Arg307Gln
  • LRG_367t1:c.920G>A
  • LRG_367t2:c.920G>A
  • LRG_367:g.49319G>A
  • LRG_367p1:p.Arg307Gln
  • LRG_367p2:p.Arg307Gln
  • NC_000002.11:g.241715306C>T
  • NM_001244008.1:c.920G>A
  • NM_004321.6:c.920G>A
  • NM_004321.7:c.920G>A
  • p.Arg307Gln
Protein change:
R307Q
Links:
dbSNP: rs1064793161
NCBI 1000 Genomes Browser:
rs1064793161
Molecular consequence:
  • NM_001244008.2:c.920G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001320705.2:c.920G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330289.2:c.920G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330290.2:c.920G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379631.1:c.920G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379632.1:c.920G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379633.1:c.920G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379634.1:c.920G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379635.1:c.920G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379636.1:c.920G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379637.1:c.920G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379638.1:c.920G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379639.1:c.920G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379640.1:c.920G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379641.1:c.920G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379642.1:c.920G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379645.1:c.920G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379646.1:c.920G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379648.1:c.920G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379649.1:c.920G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379650.1:c.920G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379651.1:c.920G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379653.1:c.920G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004321.8:c.920G>A - 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
SCV000586758Groupe Hospitalier Pitie Salpetriere, UF Genomique du Developpement,Assistance Publique Hopitaux de Pariscriteria provided, single submitter
Pathogenic
(Jan 6, 2017)
de novoclinical testing

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

SCV001164442Broad Institute Rare Disease Group, Broad Institutecriteria provided, single submitter
Likely pathogenic
(Dec 3, 2018)
de novoresearch

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

SCV001426722SIB Swiss Institute of Bioinformaticscriteria provided, single submitter
Likely 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 providednot providednot providedclinical testing, research
not providedunknownunknownnot providednot providednot providednot providednot providedcuration

Citations

PubMed

Using medical exome sequencing to identify the causes of neurodevelopmental disorders: Experience of 2 clinical units and 216 patients.

Chérot E, Keren B, Dubourg C, Carré W, Fradin M, Lavillaureix A, Afenjar A, Burglen L, Whalen S, Charles P, Marey I, Heide S, Jacquette A, Heron D, Doummar D, Rodriguez D, Billette de Villemeur T, Moutard ML, Guët A, Xavier J, Périsse D, Cohen D, et al.

Clin Genet. 2018 Mar;93(3):567-576. doi: 10.1111/cge.13102. Epub 2017 Oct 4.

PubMed [citation]
PMID:
28708303

Novel De Novo Mutations in KIF1A as a Cause of Hereditary Spastic Paraplegia With Progressive Central Nervous System Involvement.

Hotchkiss L, Donkervoort S, Leach ME, Mohassel P, Bharucha-Goebel DX, Bradley N, Nguyen D, Hu Y, Gurgel-Giannetti J, Bönnemann CG.

J Child Neurol. 2016 Aug;31(9):1114-9. doi: 10.1177/0883073816639718. Epub 2016 Mar 31.

PubMed [citation]
PMID:
27034427
PMCID:
PMC5030766
See all PubMed Citations (4)

Details of each submission

From Groupe Hospitalier Pitie Salpetriere, UF Genomique du Developpement,Assistance Publique Hopitaux de Paris, SCV000586758.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (2)

Description

neurodegenerative syndrome; Intellectual disability; hypotonia; cerebellar atrophy; optic nerve atrophy; congenital retinal dystrophy; pyramidal syndrome (Rossolimo and Babinsky signs)

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1de novoyesnot providednot providednot provided1not providednot providednot provided

From Broad Institute Rare Disease Group, Broad Institute, SCV001164442.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearch PubMed (1)

Description

The heterozyous p.Arg307Gln variant in KIF1A was identified by our study in one individual with GLUT1 deficiency syndrome. Trio exome analysis showed this variant to be de novo. This variant was absent from large population studies and is predicted to shorten the length of the protein by three residues due to an in-frame deletion. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, although additional studies are required to fully establish its clinical significance, the p.Glu209_Pro211del variant is likely pathogenic. ACMG/AMP Criteria applied: PM2, PS2, PM4, PP3 (Richards 2015).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1de novoyesnot providednot providednot providednot providednot providednot providednot provided

From SIB Swiss Institute of Bioinformatics, SCV001426722.1

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

Description

This variant is interpreted as likely 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); 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); De novo (paternity and maternity confirmed) (PS2).

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

Last Updated: Dec 4, 2021

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