rs113313967
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_138477.4(CDAN1):c.1860+5G>A variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000156 in 1,614,176 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_138477.4 splice_donor_5th_base, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDAN1 | NM_138477.4 | c.1860+5G>A | splice_donor_5th_base_variant, intron_variant | ENST00000356231.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDAN1 | ENST00000356231.4 | c.1860+5G>A | splice_donor_5th_base_variant, intron_variant | 1 | NM_138477.4 | P1 | |||
CDAN1 | ENST00000643434.1 | c.*1038+5G>A | splice_donor_5th_base_variant, intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.000499 AC: 76AN: 152170Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000211 AC: 53AN: 251476Hom.: 0 AF XY: 0.000177 AC XY: 24AN XY: 135910
GnomAD4 exome AF: 0.000118 AC: 172AN: 1461888Hom.: 1 Cov.: 35 AF XY: 0.000124 AC XY: 90AN XY: 727248
GnomAD4 genome ? AF: 0.000525 AC: 80AN: 152288Hom.: 0 Cov.: 33 AF XY: 0.000564 AC XY: 42AN XY: 74460
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 29, 2022 | In-silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 31589614, 26147798, 16098079) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 30, 2022 | This sequence change falls in intron 12 of the CDAN1 gene. It does not directly change the encoded amino acid sequence of the CDAN1 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (rs113313967, gnomAD 0.2%). This variant has been observed in individual(s) with dyserythropoietic anemia type 1 (PMID: 16098079). This variant is also known as IVS-12+5G > A. ClinVar contains an entry for this variant (Variation ID: 3181). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in inclusion of intron 12 and introduces a premature termination codon (PMID: 16098079). The resulting mRNA is expected to undergo nonsense-mediated decay. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Congenital dyserythropoietic anemia, type I Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 01, 2005 | - - |
Anemia, congenital dyserythropoietic, type 1a Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Jun 15, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at