20-50891406-T-TA

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM4 PP5

The NM_001282531.3(ADNP):c.3307_3308insT(p.Ter1103LeufsTer80) variant causes a frameshift, stop lost change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ADNP NM_001282531.3 frameshift, stop_lost
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.74

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Frameshift in the end of transcript resulting in stoplost. Downstream stopcodon found after 1105 codons.
• PP5: Variant 20-50891406-T-TA is Pathogenic according to our data. Variant chr20-50891406-T-TA is described in ClinVar as [Likely_pathogenic]. Clinvar id is 545057.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADNP	NM_001282531.3	c.3307_3308insT	p.Ter1103LeufsTer80	frameshift_variant, stop_lost	6/6	ENST00000621696.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADNP	ENST00000621696.5	c.3307_3308insT	p.Ter1103LeufsTer80	frameshift_variant, stop_lost	6/6	5	NM_001282531.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Pathogenic:1

Likely pathogenic, no assertion criteria provided

clinical testing

Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes

Jan 31, 2017

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1555809337; hg19: chr20-49507943;