chr12-93678776-T-G
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PVS1PS1_ModeratePM2PP5
The NM_003805.5(CRADD):c.2T>G(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.00000206 in 1,457,144 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 (no stars).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
CRADD
NM_003805.5 start_lost
NM_003805.5 start_lost
Scores
7
8
1
Clinical Significance
Conservation
PhyloP100: 6.99
Genes affected
CRADD (HGNC:2340): (CASP2 and RIPK1 domain containing adaptor with death domain) This gene encodes a protein containing a death domain (DD) motif. This protein recruits caspase 2/ICH1 to the cell death signal transduction complex, which includes tumor necrosis factor receptor 1 (TNFR1A) and RIPK1/RIP kinase, and acts in promoting apoptosis. A mutation in this gene was associated with cognitive disability. A related pseudogene is found on chromosome 3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 13 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
PS1
?
Another start lost variant in NM_003805.5 (CRADD) was described as [Pathogenic] in ClinVar as 981900
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 12-93678776-T-G is Pathogenic according to our data. Variant chr12-93678776-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 870252.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CRADD | NM_003805.5 | c.2T>G | p.Met1? | start_lost | 2/3 | ENST00000332896.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRADD | ENST00000332896.8 | c.2T>G | p.Met1? | start_lost | 2/3 | 1 | NM_003805.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248574Hom.: 0 AF XY: 0.00000743 AC XY: 1AN XY: 134616
GnomAD3 exomes
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1
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248574
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GnomAD4 exome AF: 0.00000206 AC: 3AN: 1457144Hom.: 0 Cov.: 31 AF XY: 0.00000414 AC XY: 3AN XY: 724268
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ExAC
?
AF:
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1
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Intellectual disability, moderate Pathogenic:1
Pathogenic, no assertion criteria provided | research | Department of Molecular Bıology and Genetics, Istanbul Technical University | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Uncertain
D;D;.;D;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.;D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D;D;D;D;D
PROVEAN
Pathogenic
D;D;D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D;D;D
Sift4G
Pathogenic
D;D;D;D;D
Polyphen
1.0, 0.98
.;D;.;D;D
Vest4
MutPred
Gain of MoRF binding (P = 0.034);Gain of MoRF binding (P = 0.034);Gain of MoRF binding (P = 0.034);Gain of MoRF binding (P = 0.034);Gain of MoRF binding (P = 0.034);
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at