NM_001363.5(DKC1):c.62C>T (p.Ser21Leu) AND Dyskeratosis congenita

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 10, 2023
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:: RCV002962035.3

Allele description [Variation Report for NM_001363.5(DKC1):c.62C>T (p.Ser21Leu)]

NM_001363.5(DKC1):c.62C>T (p.Ser21Leu)

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.62C>T (p.Ser21Leu)

HGVS:

NC_000023.11:g.154764944C>T
NG_009780.1:g.7189C>T
NM_001142463.3:c.62C>T
NM_001288747.2:c.62C>T
NM_001363.5:c.62C>TMANE SELECT
NP_001135935.1:p.Ser21Leu
NP_001275676.1:p.Ser21Leu
NP_001354.1:p.Ser21Leu
NP_001354.1:p.Ser21Leu
LRG_55t1:c.62C>T
LRG_55:g.7189C>T
LRG_55p1:p.Ser21Leu
NC_000023.10:g.153993219C>T
NM_001363.3:c.62C>T
NR_110021.2:n.164C>T
NR_110022.2:n.164C>T
NR_110023.2:n.164C>T

Protein change:

S21L

Molecular consequence:

NM_001142463.3:c.62C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001288747.2:c.62C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001363.5:c.62C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_110021.2:n.164C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_110022.2:n.164C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_110023.2:n.164C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Dyskeratosis congenita
Identifiers:: MONDO: MONDO:0015780; MedGen: C0265965; OMIM: PS127550

Recent activity

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endonuclease (plasmid) [Klebsiella variicola]
endonuclease (plasmid) [Klebsiella variicola]
gi|1142877550|gnl|PRJNA327903|BBD64 0|gb|AQL24094.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003279703	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 31, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004067207	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Aug 10, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003279703

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 31, 2022)

germline

clinical testing

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

SCV004067207

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Aug 10, 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, SCV003279703.1

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

Description

This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 21 of the DKC1 protein (p.Ser21Leu). This variant is present in population databases (rs782389383, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with DKC1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant 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

From Ambry Genetics, SCV004067207.2

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

Description

The c.62C>T (p.S21L) alteration is located in exon 2 (coding exon 2) of the DKC1 gene. This alteration results from a C to T substitution at nucleotide position 62, causing the serine (S) at amino acid position 21 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, 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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