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

Germline classification:: Benign/Likely benign (3 submissions)
Last evaluated:: Jan 29, 2024
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:: RCV000634503.12

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
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
SCV000755819	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Jan 29, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002535834	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Likely benign (Nov 15, 2021)	germline	curation	PubMed (7) [See all records that cite these PMIDs] 11379875, 31268371, 27622320, 29921932, 29625052, 32126783, 20008900 Citation Link,
SCV002678754	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Benign (Aug 26, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000755819

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Benign
(Jan 29, 2024)

germline

clinical testing

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

SCV002535834

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Likely benign
(Nov 15, 2021)

germline

curation

PubMed (7)
[See all records that cite these PMIDs]

Citation Link,

SCV002678754

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Benign
(Aug 26, 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, curation

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

Identification of novel DKC1 mutations in patients with dyskeratosis congenita: implications for pathophysiology and diagnosis.

Knight SW, Vulliamy TJ, Morgan B, Devriendt K, Mason PJ, Dokal I.

Hum Genet. 2001 Apr;108(4):299-303.

PubMed [citation]

PMID:: 11379875

See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000755819.7

#	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 Sema4, Sema4, SCV002535834.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (7)

#	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, SCV002678754.2

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

Description

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

#	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 3, 2024

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