Genetic Variant ADAP2:p.Leu14Val (chr17-30922054-C-G) – 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.40C>G(p.Leu14Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar 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

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.41

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.40C>G	p.Leu14Val	missense	Exon 1 of 11	NP_060874.1	Q9NPF8-1
ADAP2	NM_001346712.2		c.40C>G	p.Leu14Val	missense	Exon 1 of 11	NP_001333641.1	Q2V6Q1
ADAP2	NM_001346714.2		c.40C>G	p.Leu14Val	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.40C>G	p.Leu14Val	missense	Exon 1 of 11	ENSP00000329468.3	Q9NPF8-1
ADAP2	ENST00000580525.6	TSL:1	c.40C>G	p.Leu14Val	missense	Exon 1 of 11	ENSP00000464121.1	Q2V6Q1
ADAP2	ENST00000890570.1		c.40C>G	p.Leu14Val	missense	Exon 1 of 12	ENSP00000560629.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1121940

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

539640

African (AFR)

AF:

0.00

AC:

AN:

22930

American (AMR)

AF:

0.00

AC:

AN:

8408

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14544

East Asian (EAS)

AF:

0.00

AC:

AN:

26340

South Asian (SAS)

AF:

0.00

AC:

AN:

30628

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23512

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3506

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

947138

Other (OTH)

AF:

0.00

AC:

AN:

44934

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.055

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.086

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.73

M_CAP

Pathogenic

0.67

MetaRNN

Uncertain

0.43

MetaSVM

Benign

-0.68

MutationAssessor

Benign

2.0

PhyloP100

1.4

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-1.3

REVEL

Benign

0.24

Sift

Benign

0.12

Sift4G

Benign

0.18

Polyphen

0.96

Vest4

0.13

MutPred

0.65

Loss of helix (P = 0.0626)

MVP

0.53

MPC

0.67

ClinPred

0.74

GERP RS

4.9

PromoterAI

-0.074

Neutral

(source)

Varity_R

0.27

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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