Variant chr12-57730883-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_001122772.3(AGAP2):c.2216G>A(p.Arg739Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000497 in 1,609,248 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: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

AGAP2
NM_001122772.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.69

Variant links:

Genes affected

AGAP2 (HGNC:16921): (ArfGAP with GTPase domain, ankyrin repeat and PH domain 2) The protein encoded by this gene belongs to the centaurin gamma-like family. It mediates anti-apoptotic effects of nerve growth factor by activating nuclear phosphoinositide 3-kinase. It is overexpressed in cancer cells, and promotes cancer cell invasion. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]

AGAP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.763

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
AGAP2	NM_001122772.3 linkuse as main transcript	c.2216G>A	p.Arg739Gln	missense_variant	11/19	ENST00000547588.6	NP_001116244.1
AGAP2	NM_014770.4 linkuse as main transcript	c.1208G>A	p.Arg403Gln	missense_variant	11/18		NP_055585.1
AGAP2	XM_005268625.4 linkuse as main transcript	c.2216G>A	p.Arg739Gln	missense_variant	11/18		XP_005268682.1
AGAP2	XM_005268626.3 linkuse as main transcript	c.1208G>A	p.Arg403Gln	missense_variant	11/19		XP_005268683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGAP2	ENST00000547588.6 linkuse as main transcript	c.2216G>A	p.Arg739Gln	missense_variant	11/19	1	NM_001122772.3	ENSP00000449241	P3
AGAP2	ENST00000257897.7 linkuse as main transcript	c.1208G>A	p.Arg403Gln	missense_variant	11/18	1		ENSP00000257897	A1	Q99490-2
AGAP2	ENST00000328568.9 linkuse as main transcript	c.1808G>A	p.Arg603Gln	missense_variant	11/18	5		ENSP00000328160
AGAP2	ENST00000549129.1 linkuse as main transcript	c.284G>A	p.Arg95Gln	missense_variant	4/5	3		ENSP00000446683

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000415

AC:

AN:

241146

Hom.:

AF XY:

0.00000766

AC XY:

AN XY:

130522

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000298

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000412

AC:

AN:

1457020

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724502

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:

0.00000541

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000371

Hom.:

Bravo

AF:

0.00000756

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

Feb 17, 2022

The c.2216G>A (p.R739Q) alteration is located in exon 11 (coding exon 11) of the AGAP2 gene. This alteration results from a G to A substitution at nucleotide position 2216, causing the arginine (R) at amino acid position 739 to be replaced by a glutamine (Q). 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

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.11

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.11

.;.;T

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

D;D;D

M_CAP

Uncertain

0.11

MetaRNN

Pathogenic

0.76

D;D;D

MetaSVM

Uncertain

-0.015

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-3.1

D;D;D

REVEL

Pathogenic

0.69

Sift

Uncertain

0.014

D;D;T

Sift4G

Benign

0.15

T;T;D

Polyphen

0.97

D;D;.

Vest4

0.60

MutPred

0.43

.;Loss of methylation at R739 (P = 0.0284);.;

MVP

0.82

MPC

1.5

ClinPred

0.99

GERP RS

5.0

gMVP

0.63

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