Genetic Variant ADAP2:p.Asp27Asn (chr17-30922093-G-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_018404.3(ADAP2):c.79G>A(p.Asp27Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000173 in 1,099,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

ADAP2
NM_018404.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.75

Publications

1 publications found

Variant links:

Genes affected

ADAP2 (HGNC:16487): (ArfGAP with dual PH domains 2) The protein encoded by this gene binds beta-tubulin and increases the stability of microtubules. The encoded protein can also translocate to the cell membrane and bind phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3) and inositol 1,3,4,5-tetrakisphosphate (InsP4). In addition, this protein is a GTPase-activating protein for ADP ribosylation factor 6 and may be able to block the entry of some RNA viruses. [provided by RefSeq, Oct 2016]

ADAP2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.917

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAP2	NM_018404.3 link	c.79G>A	p.Asp27Asn	missense_variant	Exon 1 of 11	ENST00000330889.8	NP_060874.1	Q9NPF8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAP2	ENST00000330889.8 link	c.79G>A	p.Asp27Asn	missense_variant	Exon 1 of 11	1	NM_018404.3	ENSP00000329468.3		Q9NPF8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000173

AC:

AN:

1099408

Hom.:

Cov.:

AF XY:

0.0000191

AC XY:

AN XY:

524194

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22698

American (AMR)

AF:

0.00

AC:

AN:

8182

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14254

East Asian (EAS)

AF:

0.00

AC:

AN:

25986

South Asian (SAS)

AF:

0.00

AC:

AN:

26392

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22578

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3212

European-Non Finnish (NFE)

AF:

0.0000204

AC:

AN:

932094

Other (OTH)

AF:

0.00

AC:

AN:

44012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

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

Apr 24, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.79G>A (p.D27N) alteration is located in exon 1 (coding exon 1) of the ADAP2 gene. This alteration results from a G to A substitution at nucleotide position 79, causing the aspartic acid (D) at amino acid position 27 to be replaced by an asparagine (N). 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

Pathogenic

0.96

BayesDel_addAF

Benign

-0.013

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.36

T;T;.

Eigen

Pathogenic

0.72

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.86

LIST_S2

Pathogenic

0.99

D;D;D

M_CAP

Pathogenic

0.83

MetaRNN

Pathogenic

0.92

D;D;D

MetaSVM

Uncertain

0.22

MutationAssessor

Pathogenic

4.4

H;.;.

PhyloP100

3.8

PrimateAI

Pathogenic

0.90

PROVEAN

Uncertain

-3.3

D;.;.

REVEL

Uncertain

0.58

Sift

Uncertain

0.0040

D;.;.

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.52

MutPred

0.90

Gain of sheet (P = 0.1945);Gain of sheet (P = 0.1945);Gain of sheet (P = 0.1945);

MVP

0.69

MPC

0.95

ClinPred

0.99

GERP RS

4.0

PromoterAI

-0.068

Neutral

(source)

Varity_R

0.50

gMVP

0.72

Mutation Taster

=79/21

polymorphism

(source)

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

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17-30922093-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over