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NM_001363.5(DKC1):c.1226C>T (p.Pro409Leu) AND multiple conditions

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Apr 22, 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:
RCV002371802.1

Allele description

NM_001363.5(DKC1):c.1226C>T (p.Pro409Leu)

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.1226C>T (p.Pro409Leu)
HGVS:
  • NC_000023.11:g.154774672C>T
  • NG_009780.1:g.16917C>T
  • NM_001142463.3:c.1226C>T
  • NM_001288747.2:c.1226C>T
  • NM_001363.5:c.1226C>TMANE SELECT
  • NP_001135935.1:p.Pro409Leu
  • NP_001275676.1:p.Pro409Leu
  • NP_001354.1:p.Pro409Leu
  • LRG_55t1:c.1226C>T
  • LRG_55:g.16917C>T
  • NC_000023.10:g.154002947C>T
  • NM_001363.3:c.1226C>T
  • NR_110021.2:n.1805C>T
  • NR_110022.2:n.1924C>T
  • NR_110023.2:n.1698C>T
  • O60832:p.Pro409Leu
Protein change:
P409L
Links:
UniProtKB: O60832#VAR_063825; UniProtKB/Swiss-Prot: VAR_063825; dbSNP: rs121912289
NCBI 1000 Genomes Browser:
rs121912289
Molecular consequence:
  • NM_001142463.3:c.1226C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001288747.2:c.1226C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001363.5:c.1226C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_110021.2:n.1805C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_110022.2:n.1924C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_110023.2:n.1698C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Observations:
1

Condition(s)

Name:
Dyskeratosis congenita
Identifiers:
MONDO: MONDO:0015780; MedGen: C0265965; OMIM: PS127550
Name:
Inborn genetic diseases
Identifiers:
MeSH: D030342; MedGen: C0950123

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002667543Ambry Genetics
criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)		Likely pathogenic
(Apr 22, 2022) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

Identification of a novel mutation and a de novo mutation in DKC1 in two Chinese pedigrees with Dyskeratosis congenita.

Ding YG, Zhu TS, Jiang W, Yang Y, Bu DF, Tu P, Zhu XJ, Wang BX.

J Invest Dermatol. 2004 Sep;123(3):470-3.

PubMed [citation]
PMID:
15304085

Details of each submission

From Ambry Genetics, SCV002667543.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

The p.P409L variant (also known as c.1226C>T), located in coding exon 12 of the DKC1 gene, results from a C to T substitution at nucleotide position 1226. The proline at codon 409 is replaced by leucine, an amino acid with similar properties. This alteration has been found to segregate among multiple hemizygous males in the same family who had a classical dyskeratosis congenita triad of features (Ding YG et al. J Invest Dermatol, 2004 Sep;123:470-3). This missense alteration is located in a region that has a low rate of benign missense variation (Lek M et al. Nature. 2016 Aug 18;536(7616):285-91; DECIPHER: Database of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources. Firth H.V. et al. 2009. Am.J.Hum.Genet. 84, 524-533 (DOI: dx.doi.org/10/1016/j.ajhg.2009.03.010)). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Nov 29, 2022