NM_001134831.2(AHI1):c.3474del (p.Glu1158fs) AND Familial aplasia of the vermis

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 2, 2024
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:: RCV003598272.1

Allele description

NM_001134831.2(AHI1):c.3474del (p.Glu1158fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

6q23.3

Genomic location:

Preferred name:

NM_001134831.2(AHI1):c.3474del (p.Glu1158fs)

HGVS:

NC_000006.12:g.135300512del
NG_008643.2:g.202255del
NM_001134830.2:c.3474del
NM_001134831.2:c.3474delMANE SELECT
NM_001350503.2:c.3474del
NM_001350504.2:c.3474del
NM_017651.5:c.3474del
NP_001128302.1:p.Glu1158fs
NP_001128303.1:p.Glu1158fs
NP_001337432.1:p.Glu1158fs
NP_001337433.1:p.Glu1158fs
NP_060121.3:p.Glu1158fs
NC_000006.11:g.135621649del
NC_000006.11:g.135621650del

Protein change:

E1158fs

Molecular consequence:

NM_001134830.2:c.3474del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001134831.2:c.3474del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001350503.2:c.3474del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001350504.2:c.3474del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_017651.5:c.3474del - 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
SCV004378281	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 2, 2024)	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

SCV004378281

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 2, 2024)

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, SCV004378281.1

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

Description

This sequence change creates a premature translational stop signal (p.Glu1158Aspfs*3) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with AHI1-related conditions. For these reasons, this variant has been classified as Pathogenic.

#	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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