NM_014985.3(CEP152):c.794A>C (p.Gln265Pro) AND Primary autosomal recessive microcephaly 9

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

Germline classification:: Conflicting classifications of pathogenicity (2 submissions)
Last evaluated:: Jul 24, 2014
Review status:: criteria provided, conflicting classifications

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:: RCV000000072.5

Allele description

NM_014985.3(CEP152):c.794A>C (p.Gln265Pro)

Gene:

CEP152:centrosomal protein 152 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q21.1

Genomic location:

Preferred name:

NM_014985.3(CEP152):c.794A>C (p.Gln265Pro)

HGVS:

NC_000015.10:g.48793359T>G
NG_027518.1:g.22788A>C
NM_001194998.1:c.794A>C
NM_014985.3:c.794A>C
NP_001181927.1:p.Gln265Pro
NP_055800.2:p.Gln265Pro
NC_000015.9:g.49085556T>G
O94986:p.Gln265Pro

Protein change:

Q265P; GLN265PRO

Links:

UniProtKB: O94986#VAR_063813; OMIM: 613529.0001; dbSNP: rs267606717

NCBI 1000 Genomes Browser:

rs267606717

Allele Frequency:

0.00002(G)

Molecular consequence:

NM_001194998.1:c.794A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Primary autosomal recessive microcephaly 9 (MCPH9)
Identifiers:: MedGen: C3553886; Orphanet: 2512; OMIM: 614852

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000020215	OMIM	no assertion criteria provided	Pathogenic (Jul 9, 2010)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000192745	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jul 24, 2014)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000020215

OMIM

no assertion criteria provided

Pathogenic
(Jul 9, 2010)

germline

literature only

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

SCV000192745

Genetic Services Laboratory, University of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jul 24, 2014)

germline

clinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Mutations in centrosomal protein CEP152 in primary microcephaly families linked to MCPH4.

Guernsey DL, Jiang H, Hussin J, Arnold M, Bouyakdan K, Perry S, Babineau-Sturk T, Beis J, Dumas N, Evans SC, Ferguson M, Matsuoka M, Macgillivray C, Nightingale M, Patry L, Rideout AL, Thomas A, Orr A, Hoffmann I, Michaud JL, Awadalla P, Meek DC, et al.

Am J Hum Genet. 2010 Jul 9;87(1):40-51. doi: 10.1016/j.ajhg.2010.06.003.

PubMed [citation]

PMID:: 20598275
PMCID:: PMC2896783

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From OMIM, SCV000020215.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In 2 unrelated patients from eastern Canada with autosomal recessive primary microcephaly-9 (MCPH9; 614852), Guernsey et al. (2010) identified a homozygous A-to-C transversion in the CEP152 gene, resulting in a gln265-to-pro (Q265P) substitution predicted to occur in a conserved residue in a coiled-coiled region important for organizing chromosomes for cell division. A third unrelated affected patient was compound heterozygous for the Q265P mutation and a C-to-T transition, resulting in an arg987-to-ter (R987X; 613529.0002) substitution that was predicted to result in a truncated protein missing 668 amino acids from the C terminus. In vitro functional expression studies in human osteosarcoma-derived cells showed that the R987X-mutant protein could not be detected in centrosomes, whereas the wildtype and Q265P-mutant proteins could both be detected.

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

From Genetic Services Laboratory, University of Chicago, SCV000192745.1

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

#	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		not provided	not provided	not provided	not provided

Last Updated: Mar 30, 2018

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