rs786205074
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_ModeratePM2PP3PP5_Moderate
The NM_001033855.3(DCLRE1C):c.780+1delG variant causes a splice donor, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,308 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_001033855.3 splice_donor, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152190Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251460Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135898
GnomAD4 exome Cov.: 33
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152308Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74466
ClinVar
Submissions by phenotype
Severe combined immunodeficiency due to DCLRE1C deficiency Pathogenic:2
Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This sequence change creates a premature translational stop signal (p.Ala261Glnfs*24) in the DCLRE1C gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DCLRE1C are known to be pathogenic (PMID: 21664875, 26123418). This variant is present in population databases (rs762696311, ExAC 0.003%). This variant has been observed in individual(s) with severe combined immunodeficiency (PMID: 11336668). This variant is also known as c.780+1delG and G818. ClinVar contains an entry for this variant (Variation ID: 4671). For these reasons, this variant has been classified as Pathogenic. -
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at