NM_025099.6(CTC1):c.2472del (p.Ala825fs) AND Dyskeratosis congenita

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 14, 2024
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:: RCV003530584.2

Allele description [Variation Report for NM_025099.6(CTC1):c.2472del (p.Ala825fs)]

NM_025099.6(CTC1):c.2472del (p.Ala825fs)

Gene:

CTC1:CST telomere replication complex component 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_025099.6(CTC1):c.2472del (p.Ala825fs)

HGVS:

NC_000017.11:g.8231732del
NG_032148.2:g.21367del
NM_001411067.1:c.2472del
NM_025099.6:c.2472delMANE SELECT
NP_001397996.1:p.Ala825fs
NP_079375.3:p.Ala825fs
LRG_1124t1:c.2472del
LRG_1124:g.21367del
LRG_1124p1:p.Ala825fs
NC_000017.10:g.8135047del
NC_000017.10:g.8135050del
NR_046431.2:n.2387del

Protein change:

A825fs

Molecular consequence:

NM_001411067.1:c.2472del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_025099.6:c.2472del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_046431.2:n.2387del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Dyskeratosis congenita
Identifiers:: MONDO: MONDO:0015780; MedGen: C0265965; OMIM: PS127550

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004260010	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 14, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22267198, 22387016, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004260010

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 14, 2024)

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 CTC1, encoding conserved telomere maintenance component 1, cause Coats plus.

Anderson BH, Kasher PR, Mayer J, Szynkiewicz M, Jenkinson EM, Bhaskar SS, Urquhart JE, Daly SB, Dickerson JE, O'Sullivan J, Leibundgut EO, Muter J, Abdel-Salem GM, Babul-Hirji R, Baxter P, Berger A, Bonafé L, Brunstom-Hernandez JE, Buckard JA, Chitayat D, Chong WK, Cordelli DM, et al.

Nat Genet. 2012 Jan 22;44(3):338-42. doi: 10.1038/ng.1084.

PubMed [citation]

PMID:: 22267198

Mutations in CTC1, encoding the CTS telomere maintenance complex component 1, cause cerebroretinal microangiopathy with calcifications and cysts.

Polvi A, Linnankivi T, Kivelä T, Herva R, Keating JP, Mäkitie O, Pareyson D, Vainionpää L, Lahtinen J, Hovatta I, Pihko H, Lehesjoki AE.

Am J Hum Genet. 2012 Mar 9;90(3):540-9. doi: 10.1016/j.ajhg.2012.02.002. Epub 2012 Mar 1.

PubMed [citation]

PMID:: 22387016
PMCID:: PMC3309194

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004260010.1

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

Description

This sequence change creates a premature translational stop signal (p.Ala825Leufs*59) in the CTC1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CTC1 are known to be pathogenic (PMID: 22267198, 22387016). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CTC1-related conditions. 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: Sep 29, 2024

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