NM_006031.6(PCNT):c.5059_5060del (p.Asn1687fs) AND Microcephalic osteodysplastic primordial dwarfism type II

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 3, 2021
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:: RCV001844423.2

Allele description [Variation Report for NM_006031.6(PCNT):c.5059_5060del (p.Asn1687fs)]

NM_006031.6(PCNT):c.5059_5060del (p.Asn1687fs)

Gene:

PCNT:pericentrin [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

21q22.3

Genomic location:

Preferred name:

NM_006031.6(PCNT):c.5059_5060del (p.Asn1687fs)

HGVS:

NC_000021.9:g.46402427_46402428del
NG_008961.2:g.83306_83307del
NM_001315529.2:c.4705_4706del
NM_006031.6:c.5059_5060delMANE SELECT
NP_001302458.1:p.Asn1569fs
NP_006022.3:p.Asn1687fs
NC_000021.8:g.47822341_47822342del
NM_006031.5:c.5059_5060delAA

Protein change:

N1569fs

Links:

dbSNP: rs2147504920

NCBI 1000 Genomes Browser:

rs2147504920

Molecular consequence:

NM_001315529.2:c.4705_4706del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_006031.6:c.5059_5060del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: Microcephalic osteodysplastic primordial dwarfism type II (MOPD2)
Synonyms:: MOPD II; OSTEODYSPLASTIC PRIMORDIAL DWARFISM, TYPE II; Microcephalic osteodysplastic primordial dwarfism type 2; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008872; MedGen: C0432246; Orphanet: 2637; OMIM: 210720

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002103304	Human Genetics Unit, University Of Colombo	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 3, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 18174396, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002103304

Human Genetics Unit, University Of Colombo

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 3, 2021)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
Sinhalese	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in the pericentrin (PCNT) gene cause primordial dwarfism.

Rauch A, Thiel CT, Schindler D, Wick U, Crow YJ, Ekici AB, van Essen AJ, Goecke TO, Al-Gazali L, Chrzanowska KH, Zweier C, Brunner HG, Becker K, Curry CJ, Dallapiccola B, Devriendt K, Dörfler A, Kinning E, Megarbane A, Meinecke P, Semple RK, Spranger S, et al.

Science. 2008 Feb 8;319(5864):816-9. doi: 10.1126/science.1151174. Epub 2008 Jan 3.

PubMed [citation]

PMID:: 18174396

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 Human Genetics Unit, University Of Colombo, SCV002103304.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Sinhalese	1	not provided	not provided	clinical testing	PubMed (2)

Description

The variant, denoted as c.5059_5060delAA at cDNA level, is located in exon 27 of the PCNT gene. At protein level, it substitutes the Glutamine resulting a premature Stop codon at position 11 of the new reading frame. This frameshift predicted to cause non-sense mediated decay of mRNA leading to loss of PCNT protein. Bi-allelic loss of function in PCNT gene is a known mechanism of the disease MICROCEPHALIC OSTEODYSPLASTIC PRIMORDIAL DWARFISM, TYPE II(PMID:18174396 ). This variant is not found in global population frequency databases or in our internal exome database and found in trans with a pathogenic variant in an affected individual. Hence this variant is classified as a pathogenic variant according to the following ACMG guidelines. PVS1, PM2, PM3.

#	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

Last Updated: Dec 24, 2023

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