NM_001363.5(DKC1):c.915+10G>A AND Dyskeratosis congenita

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Sep 30, 2021
Review status:: criteria provided, conflicting classifications

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:: RCV002066121.7

Allele description [Variation Report for NM_001363.5(DKC1):c.915+10G>A]

NM_001363.5(DKC1):c.915+10G>A

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.915+10G>A

HGVS:

NC_000023.11:g.154769320G>A
NG_009780.1:g.11565G>A
NM_001142463.3:c.915+10G>A
NM_001288747.2:c.915+10G>A
NM_001363.5:c.915+10G>AMANE SELECT
LRG_55t1:c.915+10G>A
LRG_55:g.11565G>A
NC_000023.10:g.153997595G>A
NC_000023.10:g.153997595G>A
NM_001363.3:c.915+10G>A
NM_001363.4:c.915+10G>A

Links:

dbSNP: rs1603429509

NCBI 1000 Genomes Browser:

rs1603429509

Molecular consequence:

NM_001142463.3:c.915+10G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001288747.2:c.915+10G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001363.5:c.915+10G>A - intron variant - [Sequence Ontology: SO:0001627]

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
SCV002362930	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely benign (Sep 30, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002684831	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Dec 15, 2014)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002362930

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely benign
(Sep 30, 2021)

germline

clinical testing

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

SCV002684831

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Dec 15, 2014)

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, SCV002362930.2

#	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 Ambry Genetics, SCV002684831.2

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

Description

The c.915+10G>A intronic variant results from a G to A substitution 10 nucleotides after coding exon 9 in the DKC1 gene. This variant was identified in a male tested for dyskeratosis congenita in our laboratory and familial testing indicated the alteration was maternally inherited; however, specifc clinical information was not provided. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples with coverage at this position. This nucleotide position is not well conserved in available vertebrate species. In addition, A is the reference nucleotide in at least 5 species. Using the BDGP and ESEfinder splice site prediction tools, this alteration may strengthen a cryptic alternate donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this variant 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 24, 2024

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