NM_014679.5(CEP57):c.185C>T (p.Pro62Leu) AND Mosaic variegated aneuploidy syndrome 2

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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 11, 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:: RCV001954463.5

Allele description

NM_014679.5(CEP57):c.185C>T (p.Pro62Leu)

Gene:

CEP57:centrosomal protein 57 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q21

Genomic location:

Preferred name:

NM_014679.5(CEP57):c.185C>T (p.Pro62Leu)

HGVS:

NC_000011.10:g.95799371C>T
NG_029829.1:g.13911C>T
NM_001243776.2:c.158C>T
NM_001243777.2:c.185C>T
NM_001363604.2:c.104C>T
NM_014679.5:c.185C>TMANE SELECT
NP_001230705.1:p.Pro53Leu
NP_001230706.1:p.Pro62Leu
NP_001350533.1:p.Pro35Leu
NP_055494.2:p.Pro62Leu
LRG_526:g.13911C>T
NC_000011.9:g.95532535C>T

Protein change:

P35L

Links:

dbSNP: rs2135260052

NCBI 1000 Genomes Browser:

rs2135260052

Molecular consequence:

NM_001243776.2:c.158C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001243777.2:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001363604.2:c.104C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_014679.5:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Mosaic variegated aneuploidy syndrome 2 (MVA2)
Identifiers:: MONDO: MONDO:0013582; MedGen: C3279843; Orphanet: 1052; OMIM: 614114

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002195006	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 11, 2023)	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

SCV002195006

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 11, 2023)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV002195006.3

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

Description

This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 62 of the CEP57 protein (p.Pro62Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CEP57-related conditions. ClinVar contains an entry for this variant (Variation ID: 1418901). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CEP57 protein function with a positive predictive value of 80%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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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