NM_003504.5(CDC45):c.165G>A (p.Trp55Ter) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 24, 2022
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:: RCV003867467.1

Allele description [Variation Report for NM_003504.5(CDC45):c.165G>A (p.Trp55Ter)]

NM_003504.5(CDC45):c.165G>A (p.Trp55Ter)

Gene:

CDC45:cell division cycle 45 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q11.21

Genomic location:

Preferred name:

NM_003504.5(CDC45):c.165G>A (p.Trp55Ter)

HGVS:

NC_000022.11:g.19481006G>A
NG_052958.1:g.6181G>A
NM_001178010.2:c.165G>A
NM_001178011.2:c.165G>A
NM_001369291.1:c.129G>A
NM_003504.5:c.165G>AMANE SELECT
NP_001171481.1:p.Trp55Ter
NP_001171482.1:p.Trp55Ter
NP_001356220.1:p.Trp43Ter
NP_003495.1:p.Trp55Ter
NC_000022.10:g.19468529G>A
NR_161281.1:n.214G>A

Protein change:

W43*

Molecular consequence:

NR_161281.1:n.214G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001178010.2:c.165G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001178011.2:c.165G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001369291.1:c.129G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_003504.5:c.165G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004672881	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 24, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 27374770, 30986546, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004672881

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 24, 2022)

germline

clinical testing

PubMed (3)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in CDC45, Encoding an Essential Component of the Pre-initiation Complex, Cause Meier-Gorlin Syndrome and Craniosynostosis.

Fenwick AL, Kliszczak M, Cooper F, Murray J, Sanchez-Pulido L, Twigg SR, Goriely A, McGowan SJ, Miller KA, Taylor IB, Logan C; WGS500 Consortium., Bozdogan S, Danda S, Dixon J, Elsayed SM, Elsobky E, Gardham A, Hoffer MJ, Koopmans M, McDonald-McGinn DM, Santen GW, et al.

Am J Hum Genet. 2016 Jul 7;99(1):125-38. doi: 10.1016/j.ajhg.2016.05.019. Epub 2016 Jun 30.

PubMed [citation]

PMID:: 27374770
PMCID:: PMC5005452

Further delineation of CDC45-related Meier-Gorlin syndrome with craniosynostosis and review of literature.

Ting CY, Bhatia NS, Lim JY, Goh CJ, Vasanwala RF, Ong CC, Seow WT, Yeow VK, Ting TW, Ng IS, Jamuar SS.

Eur J Med Genet. 2020 Feb;63(2):103652. doi: 10.1016/j.ejmg.2019.04.009. Epub 2019 Apr 13. Review.

PubMed [citation]

PMID:: 30986546

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV004672881.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with CDC45-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp55*) in the CDC45 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CDC45 are known to be pathogenic (PMID: 27374770, 30986546).

#	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: Mar 5, 2024

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