NM_001244008.2(KIF1A):c.647G>A (p.Arg216His) AND Intellectual disability, autosomal dominant 9

Germline classification:
Likely pathogenic (2 submissions)
Last evaluated:
Jun 15, 2020
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:
RCV000191021.7

Allele description [Variation Report for NM_001244008.2(KIF1A):c.647G>A (p.Arg216His)]

NM_001244008.2(KIF1A):c.647G>A (p.Arg216His)

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.647G>A (p.Arg216His)
HGVS:
  • NC_000002.12:g.240785062C>T
  • NG_029724.1:g.40146G>A
  • NM_001244008.2:c.647G>AMANE SELECT
  • NM_001320705.2:c.647G>A
  • NM_001330289.2:c.647G>A
  • NM_001330290.2:c.647G>A
  • NM_001379631.1:c.647G>A
  • NM_001379632.1:c.647G>A
  • NM_001379633.1:c.647G>A
  • NM_001379634.1:c.647G>A
  • NM_001379635.1:c.647G>A
  • NM_001379636.1:c.647G>A
  • NM_001379637.1:c.647G>A
  • NM_001379638.1:c.647G>A
  • NM_001379639.1:c.647G>A
  • NM_001379640.1:c.647G>A
  • NM_001379641.1:c.647G>A
  • NM_001379642.1:c.647G>A
  • NM_001379645.1:c.647G>A
  • NM_001379646.1:c.647G>A
  • NM_001379648.1:c.647G>A
  • NM_001379649.1:c.647G>A
  • NM_001379650.1:c.647G>A
  • NM_001379651.1:c.647G>A
  • NM_001379653.1:c.647G>A
  • NM_004321.8:c.647G>A
  • NP_001230937.1:p.Arg216His
  • NP_001230937.1:p.Arg216His
  • NP_001307634.1:p.Arg216His
  • NP_001317218.1:p.Arg216His
  • NP_001317219.1:p.Arg216His
  • NP_001366560.1:p.Arg216His
  • NP_001366561.1:p.Arg216His
  • NP_001366562.1:p.Arg216His
  • NP_001366563.1:p.Arg216His
  • NP_001366564.1:p.Arg216His
  • NP_001366565.1:p.Arg216His
  • NP_001366566.1:p.Arg216His
  • NP_001366567.1:p.Arg216His
  • NP_001366568.1:p.Arg216His
  • NP_001366569.1:p.Arg216His
  • NP_001366570.1:p.Arg216His
  • NP_001366571.1:p.Arg216His
  • NP_001366574.1:p.Arg216His
  • NP_001366575.1:p.Arg216His
  • NP_001366577.1:p.Arg216His
  • NP_001366578.1:p.Arg216His
  • NP_001366579.1:p.Arg216His
  • NP_001366580.1:p.Arg216His
  • NP_001366582.1:p.Arg216His
  • NP_004312.2:p.Arg216His
  • NP_004312.2:p.Arg216His
  • LRG_367t1:c.647G>A
  • LRG_367t2:c.647G>A
  • LRG_367:g.40146G>A
  • LRG_367p1:p.Arg216His
  • LRG_367p2:p.Arg216His
  • NC_000002.11:g.241724479C>T
  • NM_001244008.1:c.647G>A
  • NM_004321.6:c.647G>A
  • NM_004321.7:c.647G>A
  • Q12756:p.Arg216His
Protein change:
R216H; ARG216HIS
Links:
UniProtKB: Q12756#VAR_075482; OMIM: 601255.0010; dbSNP: rs672601368
NCBI 1000 Genomes Browser:
rs672601368
Molecular consequence:
  • NM_001244008.2:c.647G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001320705.2:c.647G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330289.2:c.647G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330290.2:c.647G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379631.1:c.647G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379632.1:c.647G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379633.1:c.647G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379634.1:c.647G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379635.1:c.647G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379636.1:c.647G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379637.1:c.647G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379638.1:c.647G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379639.1:c.647G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379640.1:c.647G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379641.1:c.647G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379642.1:c.647G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379645.1:c.647G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379646.1:c.647G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379648.1:c.647G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379649.1:c.647G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379650.1:c.647G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379651.1:c.647G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379653.1:c.647G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004321.8:c.647G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Intellectual disability, autosomal dominant 9 (NESCAVS)
Synonyms:
Mental retardation, autosomal dominant 9; NESCAV SYNDROME
Identifiers:
MONDO: MONDO:0013656; MedGen: C5393830; OMIM: 614255

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000245999OMIM
no assertion criteria provided
Pathogenic
(Jun 1, 2015) 		germlineliterature only

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

SCV001426714SIB Swiss Institute of Bioinformatics
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Jun 15, 2020) 		unknowncuration

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only
not providedunknownunknownnot providednot providednot providednot providednot providedcuration

Citations

PubMed

De novo mutations in KIF1A cause progressive encephalopathy and brain atrophy.

Esmaeeli Nieh S, Madou MR, Sirajuddin M, Fregeau B, McKnight D, Lexa K, Strober J, Spaeth C, Hallinan BE, Smaoui N, Pappas JG, Burrow TA, McDonald MT, Latibashvili M, Leshinsky-Silver E, Lev D, Blumkin L, Vale RD, Barkovich AJ, Sherr EH.

Ann Clin Transl Neurol. 2015 Jun;2(6):623-35. doi: 10.1002/acn3.198. Epub 2015 May 1.

PubMed [citation]
PMID:
26125038
PMCID:
PMC4479523

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 OMIM, SCV000245999.4

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

Description

In a 16-year-old boy (patient 5) with NESCAV syndrome (NESCAVS; 614255), Esmaeeli Nieh et al. (2015) identified a de novo heterozygous c.647G-A transition (c.647G-A, NM_001244008) in the KIF1A gene, resulting in an arg216-to-his (R216H) substitution at a highly conserved residue in the motor domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was filtered against the dbSNP (build 137), 1000 Genomes Project, and Exome Sequencing Project (ESP6500) databases. Functional studies of this variant were not performed, but an in vitro microtubule gliding assay of a mutation at the same residue (R216C; 601255.0009) showed that the R216C mutant protein had no motility. This patient also carried a missense variant of unknown significance in the NID1 gene (T408K; 131390), which may have explained his cataracts.

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

From SIB Swiss Institute of Bioinformatics, SCV001426714.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (2)

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); Novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before (PM5).

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

Last Updated: Apr 15, 2024