Variant 17-30945047-T-A 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_018404.3(ADAP2):c.651T>A(p.Ser217Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ADAP2
NM_018404.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0200

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 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=0.15935344).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAP2	NM_018404.3 linkuse as main transcript	c.651T>A	p.Ser217Arg	missense_variant	6/11	ENST00000330889.8	NP_060874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAP2	ENST00000330889.8 linkuse as main transcript	c.651T>A	p.Ser217Arg	missense_variant	6/11	1	NM_018404.3	ENSP00000329468	A1	Q9NPF8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

250624

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135460

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000353

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461482

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727020

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:

0.00000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Sep 28, 2022

The c.651T>A (p.S217R) alteration is located in exon 6 (coding exon 6) of the ADAP2 gene. This alteration results from a T to A substitution at nucleotide position 651, causing the serine (S) at amino acid position 217 to be replaced by an arginine (R). 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

0.33

BayesDel_addAF

Benign

-0.097

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Uncertain

0.65

D;.;D;.;T

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.12

LIST_S2

Uncertain

0.90

D;D;D;D;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.16

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;.;.;.;.

MutationTaster

Benign

0.77

D;D

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-2.9

D;.;.;.;.

REVEL

Benign

0.083

Sift

Uncertain

0.026

D;.;.;.;.

Sift4G

Benign

0.13

T;D;T;T;T

Polyphen

0.011

B;.;B;.;.

Vest4

0.28

MutPred

0.58

.;.;Gain of MoRF binding (P = 0.0499);.;.;

MVP

0.49

MPC

0.93

ClinPred

0.71

GERP RS

-1.1

Varity_R

0.20

gMVP

0.59

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over