chr20-50891406-T-TA

Variant names:

• chr20-50891406-T-TA
• rs1555809337
• NM_001282531.3:c.3307dupT

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2 PM4 PP5

The NM_001282531.3(ADNP):​c.3307dupT​(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
• Publications: 0 publications found

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]

ADNP Gene-Disease associations (from GenCC):

• ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder

  Inheritance: AD, Unknown Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Illumina, Orphanet, G2P, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_001282531.3 Downstream stopcodon found after 7 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 VariationId is 545057.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282531.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADNP	NM_001282531.3	MANE Select	c.3307dupT	p.Ter1103LeufsTer80	frameshift stop_lost	Exon 6 of 6	NP_001269460.1	Q9H2P0
	ADNP	NM_001439000.1		c.3523dupT	p.Ter1175LeufsTer80	frameshift stop_lost	Exon 6 of 6	NP_001425929.1
	ADNP	NM_001282532.2		c.3307dupT	p.Ter1103LeufsTer80	frameshift stop_lost	Exon 4 of 4	NP_001269461.1	Q9H2P0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADNP	ENST00000621696.5	TSL:5 MANE Select	c.3307dupT	p.Ter1103LeufsTer80	frameshift stop_lost	Exon 6 of 6	ENSP00000483881.1	Q9H2P0
	ADNP	ENST00000349014.8	TSL:1	c.3307dupT	p.Ter1103LeufsTer80	frameshift stop_lost	Exon 4 of 4	ENSP00000342905.3	Q9H2P0
	ADNP	ENST00000371602.9	TSL:1	c.3307dupT	p.Ter1103LeufsTer80	frameshift stop_lost	Exon 3 of 3	ENSP00000360662.2	Q9H2P0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.7

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

Other links and lift over

dbSNP: rs1555809337; hg19: chr20-49507943;