rs1800533

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000620277.4(DKC1):n.2264G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,182,442 control chromosomes in the GnomAD database, including 5,806 homozygotes. There are 44,397 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.092 ( 516 hom., 3149 hem., cov: 23)

Exomes 𝑓: 0.11 ( 5290 hom. 41248 hem. )

Consequence

DKC1
ENST00000620277.4 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.43

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

DKC1-related disorder
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
dyskeratosis congenita, X-linked
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P
dyskeratosis congenita
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Hoyeraal-Hreidarsson syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DKC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant X-154776873-G-A is Benign according to our data. Variant chrX-154776873-G-A is described in ClinVar as Benign. ClinVar VariationId is 166995.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000620277.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
DKC1	NM_001363.5	MANE Select	c.*6G>A	3_prime_UTR	Exon 15 of 15	NP_001354.1
DKC1	NR_110021.2		n.2130G>A	non_coding_transcript_exon	Exon 14 of 14
DKC1	NR_110022.2		n.2249G>A	non_coding_transcript_exon	Exon 14 of 14

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
DKC1	ENST00000620277.4	TSL:1	n.2264G>A	non_coding_transcript_exon	Exon 14 of 14
DKC1	ENST00000369550.10	TSL:1 MANE Select	c.*6G>A	3_prime_UTR	Exon 15 of 15	ENSP00000358563.5
DKC1	ENST00000413910.6	TSL:5	n.*347G>A	non_coding_transcript_exon	Exon 16 of 16	ENSP00000400542.2

Frequencies

GnomAD3 genomes

AF:

0.0916

AC:

10180

AN:

111102

Hom.:

516

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0271

Gnomad AMI

AF:

0.115

Gnomad AMR

AF:

0.190

Gnomad ASJ

AF:

0.194

Gnomad EAS

AF:

0.103

Gnomad SAS

AF:

0.368

Gnomad FIN

AF:

0.0606

Gnomad MID

AF:

0.148

Gnomad NFE

AF:

0.0927

Gnomad OTH

AF:

0.118

GnomAD2 exomes

AF:

0.147

AC:

23600

AN:

161034

AF XY:

0.163

show subpopulations

Gnomad AFR exome

AF:

0.0263

Gnomad AMR exome

AF:

0.259

Gnomad ASJ exome

AF:

0.192

Gnomad EAS exome

AF:

0.101

Gnomad FIN exome

AF:

0.0673

Gnomad NFE exome

AF:

0.0950

Gnomad OTH exome

AF:

0.142

GnomAD4 exome

AF:

0.109

AC:

116583

AN:

1071289

Hom.:

5290

Cov.:

AF XY:

0.121

AC XY:

41248

AN XY:

340227

show subpopulations

African (AFR)

AF:

0.0247

AC:

641

AN:

25915

American (AMR)

AF:

0.249

AC:

8371

AN:

33639

Ashkenazi Jewish (ASJ)

AF:

0.195

AC:

3702

AN:

19004

East Asian (EAS)

AF:

0.0641

AC:

1906

AN:

29713

South Asian (SAS)

AF:

0.358

AC:

18787

AN:

52477

European-Finnish (FIN)

AF:

0.0699

AC:

2776

AN:

39737

Middle Eastern (MID)

AF:

0.245

AC:

997

AN:

4074

European-Non Finnish (NFE)

AF:

0.0896

AC:

73631

AN:

821591

Other (OTH)

AF:

0.128

AC:

5772

AN:

45139

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

3025

6051

9076

12102

15127

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2930

5860

8790

11720

14650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0915

AC:

10172

AN:

111153

Hom.:

516

Cov.:

AF XY:

0.0944

AC XY:

3149

AN XY:

33365

show subpopulations

African (AFR)

AF:

0.0271

AC:

830

AN:

30631

American (AMR)

AF:

0.190

AC:

1995

AN:

10482

Ashkenazi Jewish (ASJ)

AF:

0.194

AC:

512

AN:

2643

East Asian (EAS)

AF:

0.102

AC:

362

AN:

3548

South Asian (SAS)

AF:

0.366

AC:

919

AN:

2509

European-Finnish (FIN)

AF:

0.0606

AC:

366

AN:

6044

Middle Eastern (MID)

AF:

0.139

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.0927

AC:

4905

AN:

52891

Other (OTH)

AF:

0.116

AC:

176

AN:

1517

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

314

629

943

1258

1572

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

118

236

354

472

590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0966

Hom.:

1459

Bravo

AF:

0.0954

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (2)

Dyskeratosis congenita, X-linked (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.17

(source)

DANN

Benign

0.59

PhyloP100

-1.4

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over