NM_001363.5(DKC1):c.1240C>G (p.Gln414Glu) AND Dyskeratosis congenita, X-linked

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 15, 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:: RCV003154608.1

Allele description [Variation Report for NM_001363.5(DKC1):c.1240C>G (p.Gln414Glu)]

NM_001363.5(DKC1):c.1240C>G (p.Gln414Glu)

Gene:

DKC1:dyskerin pseudouridine synthase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq28

Genomic location:

Preferred name:

NM_001363.5(DKC1):c.1240C>G (p.Gln414Glu)

HGVS:

NC_000023.11:g.154774686C>G
NG_009780.1:g.16931C>G
NM_001142463.3:c.1240C>G
NM_001288747.2:c.1240C>G
NM_001363.5:c.1240C>GMANE SELECT
NP_001135935.1:p.Gln414Glu
NP_001275676.1:p.Gln414Glu
NP_001354.1:p.Gln414Glu
NP_001354.1:p.Gln414Glu
LRG_55t1:c.1240C>G
LRG_55:g.16931C>G
LRG_55p1:p.Gln414Glu
NC_000023.10:g.154002961C>G
NM_001363.3:c.1240C>G
NM_001363.4:c.1240C>G
NR_110021.2:n.1819C>G
NR_110022.2:n.1938C>G
NR_110023.2:n.1712C>G

Protein change:

Q414E

Molecular consequence:

NM_001142463.3:c.1240C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001288747.2:c.1240C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001363.5:c.1240C>G - missense variant - [Sequence Ontology: SO:0001583]
NR_110021.2:n.1819C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_110022.2:n.1938C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_110023.2:n.1712C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Dyskeratosis congenita, X-linked (DKCX)
Synonyms:: Zinsser-Cole-Engman Syndrome
Identifiers:: MONDO: MONDO:0010584; MedGen: C1148551; OMIM: 305000

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003843156	St. Jude Molecular Pathology, St. Jude Children's Research Hospital	criteria provided, single submitter (St. Jude Assertion Criteria 2020)	Uncertain significance (Nov 15, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003843156

St. Jude Molecular Pathology, St. Jude Children's Research Hospital

criteria provided, single submitter

(St. Jude Assertion Criteria 2020)

Uncertain significance
(Nov 15, 2022)

germline

clinical testing

Citation Link

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

Details of each submission

From St. Jude Molecular Pathology, St. Jude Children's Research Hospital, SCV003843156.1

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

Description

The DKC1 c.1240C>G (p.Gln414Glu) missense change has a maximum subpopulation frequency of 0.0025% in gnomAD v2.1.1 including one hemizygote (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function (REVEL = 0.18), but to our knowledge this prediction has not been confirmed by functional studies. Of note, all variants in exon 12 reported in the literature in individuals with dyskeratosis congenita have REVEL scores greater than 0.70. This variant has not been reported in the literature in individuals with dyskeratosis congenita. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as 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: Dec 17, 2023

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