20-50891466-C-CCAT

Variant names:

• chr20-50891466-C-CCAT
• rs764039253
• NM_001282531.3:c.3245_3247dupATG

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PM4_Supporting BS2

The NM_001282531.3(ADNP):​c.3245_3247dupATG​(p.Asp1082dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,460,418 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: ADNP NM_001282531.3 conservative_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 2.84
• 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: Likely_benign. The variant received -3 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001282531.3. Strenght limited to Supporting due to length of the change: 1aa.
• BS2: High AC in GnomAdExome4 at 16 AD,Unknown gene.

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.3245_3247dupATG	p.Asp1082dup	conservative_inframe_insertion	Exon 6 of 6	NP_001269460.1	Q9H2P0
	ADNP	NM_001439000.1		c.3461_3463dupATG	p.Asp1154dup	conservative_inframe_insertion	Exon 6 of 6	NP_001425929.1
	ADNP	NM_001282532.2		c.3245_3247dupATG	p.Asp1082dup	conservative_inframe_insertion	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.3245_3247dupATG	p.Asp1082dup	conservative_inframe_insertion	Exon 6 of 6	ENSP00000483881.1	Q9H2P0
	ADNP	ENST00000349014.8	TSL:1	c.3245_3247dupATG	p.Asp1082dup	conservative_inframe_insertion	Exon 4 of 4	ENSP00000342905.3	Q9H2P0
	ADNP	ENST00000371602.9	TSL:1	c.3245_3247dupATG	p.Asp1082dup	conservative_inframe_insertion	Exon 3 of 3	ENSP00000360662.2	Q9H2P0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000110 AC: 16 AN: 1460418 Hom.: 0 Cov.: 35 AF XY: 0.00000963 AC XY: 7 AN XY: 726598

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52042

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000144 AC: 16 AN: 1111948

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	ADNP-related disorder (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.8
Mutation Taster		=70/30	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs764039253; hg19: chr20-49508003;