18-80136017-G-T

Variant names:

• chr18-80136017-G-T
• rs368516384
• NM_014913.4:c.604G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014913.4(ADNP2):​c.604G>T​(p.Asp202Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D202N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ADNP2 NM_014913.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.545
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12391332).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADNP2	NM_014913.4	c.604G>T	p.Asp202Tyr	missense_variant	Exon 4 of 4	ENST00000262198.9	NP_055728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADNP2	ENST00000262198.9	c.604G>T	p.Asp202Tyr	missense_variant	Exon 4 of 4	1	NM_014913.4	ENSP00000262198.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	14
DANN	Benign	0.73
DEOGEN2	Benign	0.081	T;.
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.56	T;T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;.
PhyloP100		0.55
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Benign	0.086
Sift	Benign	0.040	D;D
Sift4G	Uncertain	0.042	D;T
Polyphen		0.99	D;.
Vest4		0.22
MutPred		0.31		Loss of disorder (P = 0.0179);.;
MVP		0.41
MPC		0.52
ClinPred		0.31	T
GERP RS		0.94
Varity_R		0.075
gMVP		0.54
Mutation Taster		=92/8	polymorphism

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: rs368516384; hg19: chr18-77893900; COSMIC: COSV100080952; COSMIC: COSV100080952;