NM_001363.5(DKC1):c.55C>T (p.Arg19Trp) AND Dyskeratosis congenita

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Nov 7, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV001926468.5

Allele description [Variation Report for NM_001363.5(DKC1):c.55C>T (p.Arg19Trp)]

NM_001363.5(DKC1):c.55C>T (p.Arg19Trp)

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.55C>T (p.Arg19Trp)

HGVS:

NC_000023.11:g.154764937C>T
NG_009780.1:g.7182C>T
NM_001142463.3:c.55C>T
NM_001288747.2:c.55C>T
NM_001363.3:c.55C>T
NM_001363.5:c.55C>TMANE SELECT
NP_001135935.1:p.Arg19Trp
NP_001275676.1:p.Arg19Trp
NP_001354.1:p.Arg19Trp
LRG_55t1:c.55C>T
LRG_55:g.7182C>T
NC_000023.10:g.153993212C>T
NR_110021.2:n.157C>T
NR_110022.2:n.157C>T
NR_110023.2:n.157C>T

Protein change:

R19W

Links:

dbSNP: rs782010351

NCBI 1000 Genomes Browser:

rs782010351

Molecular consequence:

NM_001142463.3:c.55C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001288747.2:c.55C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001363.5:c.55C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_110021.2:n.157C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_110022.2:n.157C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_110023.2:n.157C>T - 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
SCV002204594	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely benign (Nov 7, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003861411	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Mar 7, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002204594

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely benign
(Nov 7, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV003861411

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Mar 7, 2023)

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

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002204594.3

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

#	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

From Ambry Genetics, SCV003861411.2

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

Description

The p.R19W variant (also known as c.55C>T), located in coding exon 2 of the DKC1 gene, results from a C to T substitution at nucleotide position 55. The arginine at codon 19 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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: Nov 10, 2024

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