2-27239442-C-T
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_004341.5(CAD):c.5365C>T(p.Arg1789Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_004341.5 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CAD | NM_004341.5 | c.5365C>T | p.Arg1789Ter | stop_gained | 33/44 | ENST00000264705.9 | |
CAD | NM_001306079.2 | c.5176C>T | p.Arg1726Ter | stop_gained | 32/43 | ||
CAD | XM_047445803.1 | c.5365C>T | p.Arg1789Ter | stop_gained | 33/45 | ||
CAD | XM_006712101.4 | c.5176C>T | p.Arg1726Ter | stop_gained | 32/44 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CAD | ENST00000264705.9 | c.5365C>T | p.Arg1789Ter | stop_gained | 33/44 | 1 | NM_004341.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152170Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 251042Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135704
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461584Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 727068
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152170Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74336
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 50 Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 11, 2020 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München | Sep 08, 2017 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 29, 2022 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 374831). This premature translational stop signal has been observed in individual(s) with epileptic encephalopathy (PMID: 28007989). This variant is present in population databases (rs62130681, gnomAD 0.004%). This sequence change creates a premature translational stop signal (p.Arg1789*) in the CAD gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CAD are known to be pathogenic (PMID: 28007989, 32117025, 32820246, 33497533). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at