Variant rs2034648 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001037131.3(AGAP1):c.2011G>A(p.Val671Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 1,613,972 control chromosomes in the GnomAD database, including 257,386 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.65 ( 33870 hom., cov: 33)

Exomes 𝑓: 0.55 ( 223516 hom. )

Consequence

AGAP1
NM_001037131.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.638

Variant links:

Genes affected

AGAP1 (HGNC:16922): (ArfGAP with GTPase domain, ankyrin repeat and PH domain 1) This gene encodes a member of an ADP-ribosylation factor GTPase-activating protein family involved in membrane trafficking and cytoskeleton dynamics. This gene functions as a direct regulator of the adaptor-related protein complex 3 on endosomes. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

AGAP1 links:

AGAP1 (HGNC:):

AGAP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.932896E-7).

BP6

Variant 2-236049178-G-A is Benign according to our data. Variant chr2-236049178-G-A is described in ClinVar as [Benign]. Clinvar id is 2114466.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGAP1	NM_001037131.3 linkuse as main transcript	c.2011G>A	p.Val671Ile	missense_variant	16/18	ENST00000304032.13	NP_001032208.1	Q9UPQ3-1B2RZG9
AGAP1	NM_014914.5 linkuse as main transcript	c.1852G>A	p.Val618Ile	missense_variant	15/17		NP_055729.2	Q9UPQ3-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGAP1	ENST00000304032.13 linkuse as main transcript	c.2011G>A	p.Val671Ile	missense_variant	16/18	5	NM_001037131.3	ENSP00000307634.7		Q9UPQ3-1

Frequencies

GnomAD3 genomes

AF:

0.648

AC:

98504

AN:

152022

Hom.:

33807

Cov.:

show subpopulations

Gnomad AFR

AF:

0.877

Gnomad AMI

AF:

0.363

Gnomad AMR

AF:

0.677

Gnomad ASJ

AF:

0.456

Gnomad EAS

AF:

0.746

Gnomad SAS

AF:

0.539

Gnomad FIN

AF:

0.568

Gnomad MID

AF:

0.506

Gnomad NFE

AF:

0.530

Gnomad OTH

AF:

0.614

GnomAD3 exomes

AF:

0.604

AC:

151849

AN:

251470

Hom.:

47944

AF XY:

0.586

AC XY:

79654

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.884

Gnomad AMR exome

AF:

0.774

Gnomad ASJ exome

AF:

0.442

Gnomad EAS exome

AF:

0.749

Gnomad SAS exome

AF:

0.541

Gnomad FIN exome

AF:

0.562

Gnomad NFE exome

AF:

0.529

Gnomad OTH exome

AF:

0.573

GnomAD4 exome

AF:

0.547

AC:

798974

AN:

1461830

Hom.:

223516

Cov.:

AF XY:

0.544

AC XY:

395968

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.886

Gnomad4 AMR exome

AF:

0.763

Gnomad4 ASJ exome

AF:

0.437

Gnomad4 EAS exome

AF:

0.749

Gnomad4 SAS exome

AF:

0.541

Gnomad4 FIN exome

AF:

0.557

Gnomad4 NFE exome

AF:

0.522

Gnomad4 OTH exome

AF:

0.558

GnomAD4 genome

AF:

0.648

AC:

98623

AN:

152142

Hom.:

33870

Cov.:

AF XY:

0.648

AC XY:

48172

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.877

Gnomad4 AMR

AF:

0.678

Gnomad4 ASJ

AF:

0.456

Gnomad4 EAS

AF:

0.746

Gnomad4 SAS

AF:

0.537

Gnomad4 FIN

AF:

0.568

Gnomad4 NFE

AF:

0.530

Gnomad4 OTH

AF:

0.611

Alfa

AF:

0.539

Hom.:

40999

Bravo

AF:

0.666

TwinsUK

AF:

0.516

AC:

1912

ALSPAC

AF:

0.528

AC:

2036

ESP6500AA

AF:

0.863

AC:

3804

ESP6500EA

AF:

0.516

AC:

4439

ExAC

AF:

0.602

AC:

73073

Asia WGS

AF:

0.638

AC:

2217

AN:

3478

EpiCase

AF:

0.518

EpiControl

AF:

0.516

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.055

DANN

Benign

0.91

DEOGEN2

Benign

0.031

.;T;T;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.19

T;T;T;T;T

MetaRNN

Benign

6.9e-7

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

.;L;.;.;.

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.27

N;N;N;.;.

REVEL

Benign

0.035

Sift

Benign

0.42

T;T;T;.;.

Sift4G

Benign

0.51

T;T;T;T;T

Polyphen

0.0

B;B;.;.;.

Vest4

0.088

MPC

0.33

ClinPred

0.0030

GERP RS

0.32

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.019

gMVP

0.089

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

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