Variant 12-57731880-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001122772.3(AGAP2):c.1882G>A(p.Ala628Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000683 in 1,610,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

AGAP2
NM_001122772.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0640

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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.057483703).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
AGAP2	NM_001122772.3 linkuse as main transcript	c.1882G>A	p.Ala628Thr	missense_variant	8/19	ENST00000547588.6
AGAP2	NM_014770.4 linkuse as main transcript	c.874G>A	p.Ala292Thr	missense_variant	8/18
AGAP2	XM_005268625.4 linkuse as main transcript	c.1882G>A	p.Ala628Thr	missense_variant	8/18
AGAP2	XM_005268626.3 linkuse as main transcript	c.874G>A	p.Ala292Thr	missense_variant	8/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGAP2	ENST00000547588.6 linkuse as main transcript	c.1882G>A	p.Ala628Thr	missense_variant	8/19	1	NM_001122772.3	P3
AGAP2	ENST00000257897.7 linkuse as main transcript	c.874G>A	p.Ala292Thr	missense_variant	8/18	1		A1	Q99490-2
AGAP2	ENST00000328568.9 linkuse as main transcript	c.1474G>A	p.Ala492Thr	missense_variant	8/18	5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000822

AC:

AN:

243378

Hom.:

AF XY:

0.00000761

AC XY:

AN XY:

131392

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

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:

0.00000686

AC:

AN:

1458218

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

725172

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

Jan 31, 2022

The c.1882G>A (p.A628T) alteration is located in exon 8 (coding exon 8) of the AGAP2 gene. This alteration results from a G to A substitution at nucleotide position 1882, causing the alanine (A) at amino acid position 628 to be replaced by a threonine (T). 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

Benign

-0.28

BayesDel_noAF

Benign

-0.41

Cadd

Benign

Dann

Uncertain

1.0

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.0054

MetaRNN

Benign

0.057

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.72

N;N

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.65

N;N

REVEL

Benign

0.14

Sift

Benign

0.42

T;D

Sift4G

Benign

0.11

T;T

Polyphen

0.20

B;P

Vest4

0.15

MutPred

0.39

.;Gain of glycosylation at A628 (P = 0.0062);

MVP

0.56

MPC

0.64

ClinPred

0.14

GERP RS

4.6

gMVP

0.45

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