NM_001134831.2(AHI1):c.2660A>G (p.Lys887Arg) AND Agenesis of cerebellar vermis

Clinical significance:Uncertain significance (Last evaluated: Oct 3, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_001134831.2(AHI1):c.2660A>G (p.Lys887Arg)]

NM_001134831.2(AHI1):c.2660A>G (p.Lys887Arg)

AHI1:Abelson helper integration site 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_001134831.2(AHI1):c.2660A>G (p.Lys887Arg)
  • NC_000006.12:g.135427271T>C
  • NG_008643.2:g.75495A>G
  • NM_001134830.2:c.2660A>G
  • NM_001134831.2:c.2660A>GMANE SELECT
  • NM_001134832.2:c.2660A>G
  • NM_001350503.2:c.2660A>G
  • NM_001350504.2:c.2660A>G
  • NM_017651.4:c.2660A>G
  • NM_017651.5:c.2660A>G
  • NP_001128302.1:p.Lys887Arg
  • NP_001128303.1:p.Lys887Arg
  • NP_001128304.1:p.Lys887Arg
  • NP_001337432.1:p.Lys887Arg
  • NP_001337433.1:p.Lys887Arg
  • NP_060121.3:p.Lys887Arg
  • NP_060121.3:p.Lys887Arg
  • NC_000006.11:g.135748409T>C
Protein change:
dbSNP: rs200355875
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_001134830.2:c.2660A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001134831.2:c.2660A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001134832.2:c.2660A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350503.2:c.2660A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350504.2:c.2660A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_017651.4:c.2660A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_017651.5:c.2660A>G - missense variant - [Sequence Ontology: SO:0001583]


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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV001490117Invitaecriteria provided, single submitter
Uncertain significance
(Oct 3, 2020)
germlineclinical testing

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

Summary from all submissions

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



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]

Details of each submission

From Invitae, SCV001490117.1

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


This sequence change replaces lysine with arginine at codon 887 of the AHI1 protein (p.Lys887Arg). The lysine residue is weakly conserved and there is a small physicochemical difference between lysine and arginine. This variant is present in population databases (rs200355875, ExAC 0.02%). This variant has not been reported in the literature in individuals with AHI1-related conditions. ClinVar contains an entry for this variant (Variation ID: 906338). 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 not expected to disrupt AHI1 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.

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

Last Updated: Nov 27, 2021

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