NM_019892.6(INPP5E):c.473del (p.Gly158fs) AND Familial aplasia of the vermis

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Feb 4, 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:
RCV001853653.8

Allele description [Variation Report for NM_019892.6(INPP5E):c.473del (p.Gly158fs)]

NM_019892.6(INPP5E):c.473del (p.Gly158fs)

Gene:
INPP5E:inositol polyphosphate-5-phosphatase E [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
9q34.3
Genomic location:
Preferred name:
NM_019892.6(INPP5E):c.473del (p.Gly158fs)
HGVS:
  • NC_000009.12:g.136438952del
  • NG_016126.1:g.5858del
  • NM_001318502.2:c.473del
  • NM_019892.5:c.473delG
  • NM_019892.6:c.473delMANE SELECT
  • NP_001305431.1:p.Gly158fs
  • NP_063945.2:p.Gly158fs
  • NC_000009.11:g.139333399del
  • NC_000009.11:g.139333404del
  • NM_019892.4:c.473del
  • NM_019892.4:c.473delG
  • NM_019892.6:c.473del
Protein change:
G158fs
Links:
dbSNP: rs779450345
NCBI 1000 Genomes Browser:
rs779450345
Molecular consequence:
  • NM_001318502.2:c.473del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_019892.6:c.473del - 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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002173474Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Feb 4, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Mutations in INPP5E, encoding inositol polyphosphate-5-phosphatase E, link phosphatidyl inositol signaling to the ciliopathies.

Bielas SL, Silhavy JL, Brancati F, Kisseleva MV, Al-Gazali L, Sztriha L, Bayoumi RA, Zaki MS, Abdel-Aleem A, Rosti RO, Kayserili H, Swistun D, Scott LC, Bertini E, Boltshauser E, Fazzi E, Travaglini L, Field SJ, Gayral S, Jacoby M, Schurmans S, Dallapiccola B, et al.

Nat Genet. 2009 Sep;41(9):1032-6. doi: 10.1038/ng.423. Epub 2009 Aug 9.

PubMed [citation]
PMID:
19668216
PMCID:
PMC2746682

The diagnostic utility of exome sequencing in Joubert syndrome and related disorders.

Tsurusaki Y, Kobayashi Y, Hisano M, Ito S, Doi H, Nakashima M, Saitsu H, Matsumoto N, Miyake N.

J Hum Genet. 2013 Feb;58(2):113-5. doi: 10.1038/jhg.2012.117. Epub 2012 Oct 4. Erratum in: J Hum Genet. 2015 Oct;60(10):651. doi: 10.1038/jhg.2015.86.

PubMed [citation]
PMID:
23034536
See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002173474.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Gly158Valfs*40) in the INPP5E gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in INPP5E are known to be pathogenic (PMID: 19668216, 23034536, 23386033, 28125082). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Joubert syndrome (PMID: 28125082). ClinVar contains an entry for this variant (Variation ID: 451128). 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: Sep 29, 2024