NM_001363.5(DKC1):c.838A>C (p.Ser280Arg) AND Dyskeratosis congenita, X-linked

Germline classification:: Benign/Likely benign (3 submissions)
Last evaluated:: Apr 7, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000032203.5

Allele description [Variation Report for NM_001363.5(DKC1):c.838A>C (p.Ser280Arg)]

NM_001363.5(DKC1):c.838A>C (p.Ser280Arg)

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.838A>C (p.Ser280Arg)

HGVS:

NC_000023.11:g.154769233A>C
NG_009780.1:g.11478A>C
NM_001142463.3:c.838A>C
NM_001288747.2:c.838A>C
NM_001363.5:c.838A>CMANE SELECT
NP_001135935.1:p.Ser280Arg
NP_001275676.1:p.Ser280Arg
NP_001354.1:p.Ser280Arg
LRG_55t1:c.838A>C
LRG_55:g.11478A>C
NC_000023.10:g.153997508A>C
NM_001288747.1:c.838A>C
NM_001363.3:c.838A>C
NM_001363.4:c.838A>C
NM_001363.5:c.838A>C
NR_110021.2:n.1417A>C
NR_110022.2:n.1536A>C
NR_110023.2:n.1310A>C

Protein change:

S280R

Links:

dbSNP: rs146700772

NCBI 1000 Genomes Browser:

rs146700772

Molecular consequence:

NM_001142463.3:c.838A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001288747.2:c.838A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001363.5:c.838A>C - missense variant - [Sequence Ontology: SO:0001583]
NR_110021.2:n.1417A>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_110022.2:n.1536A>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_110023.2:n.1310A>C - 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

Recent activity

Clear Turn Off Turn On

Homo sapiens
Homo sapiens
RefSeq annotation of the human reference genome assembly

BioProject
BioProject Links for Nucleotide (Select 1034627293) (1)
BioProject
Taxonomy Links for Nucleotide (Select 2462582695) (1)
Taxonomy
Taxonomy Links for Protein (Select 916494016) (1)
Taxonomy

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000055795	GeneReviews	no classification provided	not provided	unknown	literature only	PubMed (1) [See all records that cite this PMID]
SCV002767331	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Feb 2, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002809283	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Apr 7, 2022)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000055795

GeneReviews

no classification provided

not provided

unknown

literature only

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

SCV002767331

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(Feb 2, 2022)

germline

clinical testing

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

SCV002809283

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Benign
(Apr 7, 2022)

unknown

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Dyskeratosis Congenita and Related Telomere Biology Disorders.

Savage SA, Niewisch MR.

2009 Nov 12 [updated 2023 Jan 19]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(®) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024.

PubMed [citation]

PMID:: 20301779

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From GeneReviews, SCV000055795.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	not provided	not provided	not provided	Assert pathogenicity		not provided	not provided	not provided	not provided

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV002767331.1

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

Description

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as likely benign. Following criteria are met: 0308 - Population frequency for this variant is out of keeping with known incidence of X-linked recessive dyskeratosis congenita (MIM#305000). (SB) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

#	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 Fulgent Genetics, Fulgent Genetics, SCV002809283.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

ClinVar

Relating variation to medicine