rs782576893

Variant names:

• chrX-154776813-CAAGAAGAAGAAG-C
• NM_001363.5:c.1503_1514delGAAGAAGAAGAA

Your query was ambiguous. Multiple possible variants found:

• chrX-154776813-CAAGAAGAAGAAG-C
• chrX-154776813-CAAGAAGAAGAAG-CAAG
• chrX-154776813-CAAGAAGAAGAAG-CAAGAAG
• chrX-154776813-CAAGAAGAAGAAG-CAAGAAGAAG
• chrX-154776813-CAAGAAGAAGAAG-CAAGAAGAAGAAGAAG
• chrX-154776813-CAAGAAGAAGAAG-CAAGAAGAAGAAGAAGAAG
• chrX-154776813-CAAGAAGAAGAAG-CAAGAAGAAGAAGAAGAAGAAG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001363.5(DKC1):​c.1503_1514delGAAGAAGAAGAA​(p.Lys502_Lys505del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00000092 in 1,086,846 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.2e-7 (0 hom. 0 hem.)
• Consequence: DKC1 NM_001363.5 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.53

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DKC1	NM_001363.5	c.1503_1514delGAAGAAGAAGAA	p.Lys502_Lys505del	disruptive_inframe_deletion	Exon 15 of 15	ENST00000369550.10	NP_001354.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DKC1	ENST00000369550.10	c.1503_1514delGAAGAAGAAGAA	p.Lys502_Lys505del	disruptive_inframe_deletion	Exon 15 of 15	1	NM_001363.5	ENSP00000358563.5

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 9.20e-7 AC: 1 AN: 1086846 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 356918

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000120

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-154005088;