rs1555810376
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001282531.3(ADNP):c.1222_1223del(p.Lys408ValfsTer31) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
ADNP
NM_001282531.3 frameshift
NM_001282531.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.47
Genes affected
ADNP (HGNC:15766): (activity dependent neuroprotector homeobox) Vasoactive intestinal peptide is a neuroprotective factor that has a stimulatory effect on the growth of some tumor cells and an inhibitory effect on others. This gene encodes a protein that is upregulated by vasoactive intestinal peptide and may be involved in its stimulatory effect on certain tumor cells. The encoded protein contains one homeobox and nine zinc finger domains, suggesting that it functions as a transcription factor. This gene is also upregulated in normal proliferative tissues. Finally, the encoded protein may increase the viability of certain cell types through modulation of p53 activity. Alternatively spliced transcript variants encoding the same protein have been described. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 59 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 20-50893490-CTT-C is Pathogenic according to our data. Variant chr20-50893490-CTT-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 190279.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-50893490-CTT-C is described in Lovd as [Pathogenic]. Variant chr20-50893490-CTT-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADNP | NM_001282531.3 | c.1222_1223del | p.Lys408ValfsTer31 | frameshift_variant | 6/6 | ENST00000621696.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADNP | ENST00000621696.5 | c.1222_1223del | p.Lys408ValfsTer31 | frameshift_variant | 6/6 | 5 | NM_001282531.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Eurofins-Biomnis | Dec 01, 2022 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 12, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
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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