Variant chrX-154776813-CAAGAAG-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001363.5(DKC1):c.1509_1514delGAAGAA(p.Lys504_Lys505del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0000577 in 1,195,503 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 21 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000091 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.000054 ( 0 hom. 19 hem. )

Consequence

DKC1
NM_001363.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.30

Variant links:

Genes affected

DKC1 (HGNC:2890): (dyskerin pseudouridine synthase 1) This gene functions in two distinct complexes. It plays an active role in telomerase stabilization and maintenance, as well as recognition of snoRNAs containing H/ACA sequences which provides stability during biogenesis and assembly into H/ACA small nucleolar RNA ribonucleoproteins (snoRNPs). This gene is highly conserved and widely expressed, and may play additional roles in nucleo-cytoplasmic shuttling, DNA damage response, and cell adhesion. Mutations have been associated with X-linked dyskeratosis congenita. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

DKC1 links:

DKC1 (HGNC:):

DKC1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant X-154776813-CAAGAAG-C is Benign according to our data. Variant chrX-154776813-CAAGAAG-C is described in ClinVar as [Benign]. Clinvar id is 800273.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-154776813-CAAGAAG-C is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DKC1	NM_001363.5 linkuse as main transcript	c.1509_1514delGAAGAA	p.Lys504_Lys505del	disruptive_inframe_deletion	15/15	ENST00000369550.10	NP_001354.1	O60832-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DKC1	ENST00000369550.10 linkuse as main transcript	c.1509_1514delGAAGAA	p.Lys504_Lys505del	disruptive_inframe_deletion	15/15	1	NM_001363.5	ENSP00000358563.5		O60832-1

Frequencies

GnomAD3 genomes

AF:

0.0000911

AC:

AN:

109781

Hom.:

Cov.:

AF XY:

0.0000618

AC XY:

AN XY:

32385

show subpopulations

Gnomad AFR

AF:

0.000298

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000779

AC:

AN:

128377

Hom.:

AF XY:

0.0000457

AC XY:

AN XY:

43799

show subpopulations

Gnomad AFR exome

AF:

0.000209

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000112

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000118

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000543

AC:

AN:

1085675

Hom.:

AF XY:

0.0000533

AC XY:

AN XY:

356169

show subpopulations

Gnomad4 AFR exome

AF:

0.000268

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000336

Gnomad4 SAS exome

AF:

0.0000379

Gnomad4 FIN exome

AF:

0.0000501

Gnomad4 NFE exome

AF:

0.0000456

Gnomad4 OTH exome

AF:

0.000198

GnomAD4 genome

AF:

0.0000911

AC:

AN:

109828

Hom.:

Cov.:

AF XY:

0.0000616

AC XY:

AN XY:

32442

show subpopulations

Gnomad4 AFR

AF:

0.000297

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000191

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000113

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Dyskeratosis congenita

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over