NM_001134831.2(AHI1):c.313_314del (p.Gln105fs) AND Familial aplasia of the vermis

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 6, 2023
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:: RCV003597886.1

Allele description [Variation Report for NM_001134831.2(AHI1):c.313_314del (p.Gln105fs)]

NM_001134831.2(AHI1):c.313_314del (p.Gln105fs)

Gene:

AHI1:Abelson helper integration site 1 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

6q23.3

Genomic location:

Preferred name:

NM_001134831.2(AHI1):c.313_314del (p.Gln105fs)

HGVS:

NC_000006.12:g.135466250GT[2]
NG_008643.2:g.36512CA[2]
NM_001134830.2:c.313_314del
NM_001134831.2:c.313_314delMANE SELECT
NM_001134832.2:c.313_314del
NM_001350503.2:c.313_314del
NM_001350504.2:c.313_314del
NM_017651.5:c.313_314del
NP_001128302.1:p.Gln105fs
NP_001128303.1:p.Gln105fs
NP_001128304.1:p.Gln105fs
NP_001337432.1:p.Gln105fs
NP_001337433.1:p.Gln105fs
NP_060121.3:p.Gln105fs
NC_000006.11:g.135787387_135787388del
NC_000006.11:g.135787388GT[2]

Protein change:

Q105fs

Molecular consequence:

NM_001134830.2:c.313_314del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001134831.2:c.313_314del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001134832.2:c.313_314del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001350503.2:c.313_314del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001350504.2:c.313_314del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_017651.5:c.313_314del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Familial aplasia of the vermis
Synonyms:: CEREBELLOPARENCHYMAL DISORDER IV; Joubert syndrome; Cerebelloparenchymal disorder 4; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0018772; MedGen: C0431399; Orphanet: 475; OMIM: PS213300

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004512325	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 6, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 15322546, 16453322, 28442542, 29186038, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004512325

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 6, 2023)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Abnormal cerebellar development and axonal decussation due to mutations in AHI1 in Joubert syndrome.

Ferland RJ, Eyaid W, Collura RV, Tully LD, Hill RS, Al-Nouri D, Al-Rumayyan A, Topcu M, Gascon G, Bodell A, Shugart YY, Ruvolo M, Walsh CA.

Nat Genet. 2004 Sep;36(9):1008-13. Epub 2004 Aug 22. Erratum in: Nat Genet. 2004 Oct;36(10):1126.

PubMed [citation]

PMID:: 15322546

AHI1 gene mutations cause specific forms of Joubert syndrome-related disorders.

Valente EM, Brancati F, Silhavy JL, Castori M, Marsh SE, Barrano G, Bertini E, Boltshauser E, Zaki MS, Abdel-Aleem A, Abdel-Salam GM, Bellacchio E, Battini R, Cruse RP, Dobyns WB, Krishnamoorthy KS, Lagier-Tourenne C, Magee A, Pascual-Castroviejo I, Salpietro CD, Sarco D, Dallapiccola B, et al.

Ann Neurol. 2006 Mar;59(3):527-34.

PubMed [citation]

PMID:: 16453322

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV004512325.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with AHI1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln105Valfs*4) in the AHI1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in AHI1 are known to be pathogenic (PMID: 15322546, 16453322, 28442542, 29186038).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 28, 2024

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