Genetic Variant ADAP2:p.Arg16Trp (chr17-30922060-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_018404.3(ADAP2):c.46C>T(p.Arg16Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R16G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ADAP2
NM_018404.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0750

Publications

0 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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018404.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADAP2	NM_018404.3	MANE Select	c.46C>T	p.Arg16Trp	missense	Exon 1 of 11	NP_060874.1	Q9NPF8-1
ADAP2	NM_001346712.2		c.46C>T	p.Arg16Trp	missense	Exon 1 of 11	NP_001333641.1	Q2V6Q1
ADAP2	NM_001346714.2		c.46C>T	p.Arg16Trp	missense	Exon 1 of 11	NP_001333643.1	Q9NPF8-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADAP2	ENST00000330889.8	TSL:1 MANE Select	c.46C>T	p.Arg16Trp	missense	Exon 1 of 11	ENSP00000329468.3	Q9NPF8-1
ADAP2	ENST00000580525.6	TSL:1	c.46C>T	p.Arg16Trp	missense	Exon 1 of 11	ENSP00000464121.1	Q2V6Q1
ADAP2	ENST00000890570.1		c.46C>T	p.Arg16Trp	missense	Exon 1 of 12	ENSP00000560629.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

594

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1120932

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

539036

African (AFR)

AF:

0.00

AC:

AN:

22916

American (AMR)

AF:

0.00

AC:

AN:

8384

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14520

East Asian (EAS)

AF:

0.00

AC:

AN:

26372

South Asian (SAS)

AF:

0.00

AC:

AN:

30290

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23392

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3446

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

946734

Other (OTH)

AF:

0.00

AC:

AN:

44878

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.053

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.84

M_CAP

Pathogenic

0.82

MetaRNN

Uncertain

0.65

MetaSVM

Benign

-0.64

MutationAssessor

Pathogenic

3.3

PhyloP100

0.075

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.21

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

0.96

Vest4

0.11

MutPred

0.68

Loss of disorder (P = 0.0027)

MVP

0.49

MPC

0.86

ClinPred

0.98

GERP RS

3.8

PromoterAI

0.037

Neutral

(source)

Varity_R

0.32

gMVP

0.47

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over