Variant 18-80136209-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000262198.9(ADNP2):c.796A>G(p.Ile266Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ADNP2
ENST00000262198.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.10

Variant links:

Genes affected

ADNP2 (HGNC:23803): (ADNP homeobox 2) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific. Predicted to be involved in several processes, including cellular response to oxidative stress; cellular response to retinoic acid; and positive regulation of cell growth. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ADNP2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19091216).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADNP2	NM_014913.4 linkuse as main transcript	c.796A>G	p.Ile266Val	missense_variant	4/4	ENST00000262198.9	NP_055728.1	Q6IQ32A0A024R377

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ADNP2	ENST00000262198.9 linkuse as main transcript	c.796A>G	p.Ile266Val	missense_variant	4/4	1	NM_014913.4	ENSP00000262198.3	Q6IQ32
ADNP2	ENST00000561195.1 linkuse as main transcript	c.34-11226A>G		intron_variant		3		ENSP00000467370.1	K7EPG1
ADNP2	ENST00000560752.5 linkuse as main transcript	c.*43A>G		downstream_gene_variant		5		ENSP00000453418.1	H0YM09

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 30, 2024

The c.796A>G (p.I266V) alteration is located in exon 4 (coding exon 3) of the ADNP2 gene. This alteration results from a A to G substitution at nucleotide position 796, causing the isoleucine (I) at amino acid position 266 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.025

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.062

Eigen

Benign

0.082

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.69

M_CAP

Benign

0.0040

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.9

MutationTaster

Benign

0.64

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.42

REVEL

Benign

0.078

Sift

Benign

0.12

Sift4G

Benign

0.077

Polyphen

0.93

Vest4

0.39

MutPred

0.27

Loss of catalytic residue at P268 (P = 0.0368);

MVP

0.63

MPC

0.17

ClinPred

0.48

GERP RS

4.3

Varity_R

0.040

gMVP

0.26

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over