Variant chr18-80117606-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 NM_014913.4(ADNP2):c.64A>G(p.Ile22Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,455,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 6.9e-7 ( 0 hom. )

Consequence

ADNP2
NM_014913.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.63

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=0.19941828).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADNP2	NM_014913.4 link	c.64A>G	p.Ile22Val	missense_variant	2/4	ENST00000262198.9	NP_055728.1	Q6IQ32A0A024R377
ADNP2	XM_047437351.1 link	c.-500A>G		5_prime_UTR_variant	1/4		XP_047293307.1
ADNP2	XM_011525883.3 link	c.42+22A>G		intron_variant			XP_011524185.1
ADNP2	XM_047437350.1 link	c.42+22A>G		intron_variant			XP_047293306.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADNP2	ENST00000262198.9 link	c.64A>G	p.Ile22Val	missense_variant	2/4	1	NM_014913.4	ENSP00000262198.3		Q6IQ32

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455678

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724252

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 13, 2023

The c.64A>G (p.I22V) alteration is located in exon 2 (coding exon 1) of the ADNP2 gene. This alteration results from a A to G substitution at nucleotide position 64, causing the isoleucine (I) at amino acid position 22 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

0.15

BayesDel_addAF

Benign

-0.053

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.058

T;T

Eigen

Benign

-0.085

Eigen_PC

Benign

-0.022

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.031

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.9

L;.

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.38

N;N

REVEL

Benign

0.14

Sift

Benign

0.060

T;T

Sift4G

Benign

0.17

T;T

Polyphen

0.51

P;.

Vest4

0.47

MutPred

0.42

Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);

MVP

0.56

MPC

0.21

ClinPred

0.77

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.049

gMVP

0.28

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over