NM_018451.5(CENPJ):c.3243_3246del (p.Ser1081fs) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Nov 6, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001091520.24

Allele description [Variation Report for NM_018451.5(CENPJ):c.3243_3246del (p.Ser1081fs)]

NM_018451.5(CENPJ):c.3243_3246del (p.Ser1081fs)

Gene:

CENPJ:centromere protein J [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

13q12.12

Genomic location:

Preferred name:

NM_018451.5(CENPJ):c.3243_3246del (p.Ser1081fs)

HGVS:

NC_000013.11:g.24889374_24889377del
NG_009165.2:g.38574_38577del
NM_018451.5:c.3243_3246delMANE SELECT
NP_060921.3:p.Ser1081fs
NC_000013.10:g.25463509_25463512del
NC_000013.10:g.25463512_25463515del
NM_018451.3:c.3243_3246delTCAG
NR_047594.2:n.3410_3413del

Protein change:

S1081fs

Links:

OMIM: 609279.0003; dbSNP: rs199422203

NCBI 1000 Genomes Browser:

rs199422203

Molecular consequence:

NM_018451.5:c.3243_3246del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_047594.2:n.3410_3413del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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Chain B, Voltage-gated ClC-type chloride channel eriC
Chain B, Voltage-gated ClC-type chloride channel eriC
gi|30749969|pdb|1OTT|B

Protein
Pcsk2 proprotein convertase subtilisin/kexin type 2 [Rattus norvegicus]
Pcsk2 proprotein convertase subtilisin/kexin type 2 [Rattus norvegicus]
Gene ID:25121

Gene
Conserved Domain Links for Gene (Select 79192540) (1)
Conserved Domains

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001247627	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Feb 1, 2019)	germline	clinical testing	Citation Link,
SCV004270991	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 6, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 15793586, 16900296, 20522431, 34958143, 35229910, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001247627

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Pathogenic
(Feb 1, 2019)

germline

clinical testing

Citation Link,

SCV004270991

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 6, 2023)

germline

clinical testing

PubMed (6)
[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	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A centrosomal mechanism involving CDK5RAP2 and CENPJ controls brain size.

Bond J, Roberts E, Springell K, Lizarraga SB, Scott S, Higgins J, Hampshire DJ, Morrison EE, Leal GF, Silva EO, Costa SM, Baralle D, Raponi M, Karbani G, Rashid Y, Jafri H, Bennett C, Corry P, Walsh CA, Woods CG.

Nat Genet. 2005 Apr;37(4):353-5. Epub 2005 Mar 27. Erratum in: Nat Genet. 2005 May;37(5):555. Lizarraga, Sophia [corrected to Lizarraga, Sofia B].

PubMed [citation]

PMID:: 15793586

A novel deletion mutation in CENPJ gene in a Pakistani family with autosomal recessive primary microcephaly.

Gul A, Hassan MJ, Hussain S, Raza SI, Chishti MS, Ahmad W.

J Hum Genet. 2006;51(9):760-764. doi: 10.1007/s10038-006-0017-1. Epub 2006 Aug 10.

PubMed [citation]

PMID:: 16900296

See all PubMed Citations (6)

Details of each submission

From CeGaT Center for Human Genetics Tuebingen, SCV001247627.26

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004270991.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change creates a premature translational stop signal (p.Ser1081Argfs*8) in the CENPJ gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CENPJ are known to be pathogenic (PMID: 15793586, 16900296, 20522431). This variant is present in population databases (rs199422203, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with CENPJ-related conditions (PMID: 34958143, 35229910). ClinVar contains an entry for this variant (Variation ID: 1819). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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: Oct 20, 2024

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