NM_001134831.2(AHI1):c.1997A>T (p.Asp666Val) AND Agenesis of cerebellar vermis

Clinical significance:Pathogenic (Last evaluated: Oct 7, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001051208.2

Allele description [Variation Report for NM_001134831.2(AHI1):c.1997A>T (p.Asp666Val)]

NM_001134831.2(AHI1):c.1997A>T (p.Asp666Val)

Gene:
AHI1:Abelson helper integration site 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
6q23.3
Genomic location:
Preferred name:
NM_001134831.2(AHI1):c.1997A>T (p.Asp666Val)
HGVS:
  • NC_000006.12:g.135438414T>A
  • NG_008643.2:g.64352A>T
  • NM_001134830.2:c.1997A>T
  • NM_001134831.2:c.1997A>TMANE SELECT
  • NM_001134832.2:c.1997A>T
  • NM_001350503.2:c.1997A>T
  • NM_001350504.2:c.1997A>T
  • NM_017651.4:c.1997A>T
  • NM_017651.5:c.1997A>T
  • NP_001128302.1:p.Asp666Val
  • NP_001128303.1:p.Asp666Val
  • NP_001128304.1:p.Asp666Val
  • NP_001337432.1:p.Asp666Val
  • NP_001337433.1:p.Asp666Val
  • NP_060121.3:p.Asp666Val
  • NP_060121.3:p.Asp666Val
  • NC_000006.11:g.135759552T>A
  • NM_001134831.1:c.1997A>T
Protein change:
D666V
Links:
dbSNP: rs863225147
NCBI 1000 Genomes Browser:
rs863225147
Molecular consequence:
  • NM_001134830.2:c.1997A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001134831.2:c.1997A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001134832.2:c.1997A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350503.2:c.1997A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350504.2:c.1997A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_017651.4:c.1997A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_017651.5:c.1997A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Agenesis of cerebellar vermis (JBTS)
Synonyms:
CEREBELLOPARENCHYMAL DISORDER IV; Joubert syndrome; Cerebelloparenchymal disorder 4; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0018772; MedGen: C0431399; Orphanet: 475; OMIM: PS213300; Human Phenotype Ontology: HP:0002335

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001215351Invitaecriteria provided, single submitter
Pathogenic
(Oct 7, 2020)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Joubert syndrome: a model for untangling recessive disorders with extreme genetic heterogeneity.

Bachmann-Gagescu R, Dempsey JC, Phelps IG, O'Roak BJ, Knutzen DM, Rue TC, Ishak GE, Isabella CR, Gorden N, Adkins J, Boyle EA, de Lacy N, O'Day D, Alswaid A, Ramadevi A R, Lingappa L, Lourenço C, Martorell L, Garcia-Cazorla À, Ozyürek H, Haliloğlu G, Tuysuz B, et al.

J Med Genet. 2015 Aug;52(8):514-22. doi: 10.1136/jmedgenet-2015-103087. Epub 2015 Jun 19.

PubMed [citation]
PMID:
26092869
PMCID:
PMC5082428

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001215351.2

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

Description

This sequence change replaces aspartic acid with valine at codon 666 of the AHI1 protein (p.Asp666Val). The aspartic acid residue is moderately conserved and there is a large physicochemical difference between aspartic acid and valine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of Joubert syndrome (PMID: 26092869, Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 217548). 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 AHI1 protein function. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Nov 27, 2021

Support Center