VCV000011583.12 - ClinVar

NM_001363.5(DKC1):c.109_111del (p.Leu37del)

Germline

Classification

criteria provided, single submitter. Learn more about how ClinVar calculates review status.

Likely pathogenic
Likely pathogenic (1)

1 out of 3 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001363.5(DKC1):c.109_111del (p.Leu37del)

Variation ID: 11583 Accession: VCV000011583.12

Type and length

Deletion, 3 bp

Location

Cytogenetic: Xq28 X: 154765466-154765468 (GRCh38) [ NCBI UCSC ] X: 153993741-153993743 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Apr 4, 2013	Mar 7, 2026	May 15, 2020

HGVS

Nucleotide	Protein	Molecular consequence
NM_001363.5:c.109_111del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001354.1:p.Leu37del	inframe deletion
NM_001142463.3:c.109_111del	NP_001135935.1:p.Leu37del	inframe deletion
NM_001288747.2:c.109_111del	NP_001275676.1:p.Leu37del	inframe deletion
NR_110021.2:n.688_690del		non-coding transcript variant
NR_110022.2:n.211_213del		non-coding transcript variant
NR_110023.2:n.211_213del		non-coding transcript variant
NC_000023.11:g.154765468_154765470del
NC_000023.10:g.153993743_153993745del
NG_009780.1:g.7713_7715del
LRG_55:g.7713_7715del
LRG_55t1:c.109_111del

... more HGVS ... less HGVS

Protein change

L37del

Other names

Canonical SPDI

NC_000023.11:154765465:TTCTT:TT

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA341109 OMIM: 300126.0002 dbSNP: rs137854489 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
DKC1		Little evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	642	867

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Dyskeratosis congenita, X-linked	Pathogenic (2)	no assertion criteria provided	May 1, 1998	RCV000012339.27
Dyskeratosis congenita	Likely pathogenic (1)	criteria provided, single submitter	May 15, 2020	RCV000634495.10

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Likely pathogenic (May 15, 2020) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Dyskeratosis congenita	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000755811.7 First in ClinVar: May 28, 2018 Last updated: Mar 07, 2026	Publications: PubMed (5) PubMed: 21602826‚ 22058290‚ 23660516‚ 25992652‚ 9590285 Comment: show Experimental studies have shown that this in-frame deletion results in compromised telomere maintenance, characterized by shortened telomeres and reduced telomerase activity (PMID: 22058290, 23660516, 21602826, 25992652). This variant has been reported in individuals affected with dyskeratosis congenita (PMID: 9590285, Invitae). ClinVar contains an entry for this variant (Variation ID: 11583). This variant is not present in population databases (ExAC no frequency). This variant, c.109_111delCTT, results in the deletion of 1 amino acid of the DKC1 protein (p.Leu37del), but otherwise preserves the integrity of the reading frame. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (May 01, 1998) N Not contributing to aggregate classification	no assertion criteria provided	DYSKERATOSIS CONGENITA, X-LINKED	OMIM Accession: SCV000032573.2 First in ClinVar: Apr 04, 2013 Last updated: Sep 08, 2024	Publications: PubMed (1) PubMed: 9590285 Observation: 1 Collection method: literature only Allele origin: germline Affected status: not provided more Observation 1 Collection method: literature only Allele origin: germline Affected status: not provided Comment on evidence: In a patient with dyskeratosis congenita (DKCX; 305000), Heiss et al. (1998) found deletion of nucleotides 201-203 (CTT), leading to deletion of leucine-37 from dyskerin.

not provided (-) N Not contributing to aggregate classification	no classification provided	Dyskeratosis congenita, X-linked	GeneReviews Accession: SCV000055771.2 First in ClinVar: Apr 04, 2013 Last updated: Oct 01, 2022	Publications: PubMed (1) PubMed: 20301779 BookShelf: NBK22301 BookShelf: NBK22301 Observation: 1 Collection method: literature only Allele origin: unknown Affected status: not provided Observation 1 Collection method: literature only Allele origin: unknown Affected status: not provided

Comment:

Experimental studies have shown that this in-frame deletion results in compromised telomere maintenance, characterized by shortened telomeres and reduced telomerase activity (PMID: 22058290, 23660516, 21602826, 25992652). This variant has been reported in individuals affected with dyskeratosis congenita (PMID: 9590285, Invitae). ClinVar contains an entry for this variant (Variation ID: 11583). This variant is not present in population databases (ExAC no frequency). This variant, c.109_111delCTT, results in the deletion of 1 amino acid of the DKC1 protein (p.Leu37del), but otherwise preserves the integrity of the reading frame. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Dyskeratosis Congenita and Related Telomere Biology Disorders.	Adam MP	-	2023	PMID: 20301779
Impaired Telomere Maintenance and Decreased Canonical WNT Signaling but Normal Ribosome Biogenesis in Induced Pluripotent Stem Cells from X-Linked Dyskeratosis Congenita Patients.	Gu BW	PloS one	2015	PMID: 25992652
Dyskeratosis congenita mutations in dyskerin SUMOylation consensus sites lead to impaired telomerase RNA accumulation and telomere defects.	Brault ME	Human molecular genetics	2013	PMID: 23660516
The accumulation and not the specific activity of telomerase ribonucleoprotein determines telomere maintenance deficiency in X-linked dyskeratosis congenita.	Zeng XL	Human molecular genetics	2012	PMID: 22058290
Telomere shortening and loss of self-renewal in dyskeratosis congenita induced pluripotent stem cells.	Batista LF	Nature	2011	PMID: 21602826
X-linked dyskeratosis congenita is caused by mutations in a highly conserved gene with putative nucleolar functions.	Heiss NS	Nature genetics	1998	PMID: 9590285

Text-mined citations for rs137854489 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Apr 13, 2026