chr12-57730609-T-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001122772.3(AGAP2):ā€‹c.2314A>Gā€‹(p.Thr772Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000564 in 1,612,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000066 ( 0 hom., cov: 33)
Exomes š‘“: 0.000055 ( 0 hom. )

Consequence

AGAP2
NM_001122772.3 missense

Scores

17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.50
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.088198185).
BS2
High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
AGAP2NM_001122772.3 linkuse as main transcriptc.2314A>G p.Thr772Ala missense_variant 12/19 ENST00000547588.6 NP_001116244.1
AGAP2NM_014770.4 linkuse as main transcriptc.1306A>G p.Thr436Ala missense_variant 12/18 NP_055585.1
AGAP2XM_005268625.4 linkuse as main transcriptc.2314A>G p.Thr772Ala missense_variant 12/18 XP_005268682.1
AGAP2XM_005268626.3 linkuse as main transcriptc.1306A>G p.Thr436Ala missense_variant 12/19 XP_005268683.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
AGAP2ENST00000547588.6 linkuse as main transcriptc.2314A>G p.Thr772Ala missense_variant 12/191 NM_001122772.3 ENSP00000449241 P3
AGAP2ENST00000257897.7 linkuse as main transcriptc.1306A>G p.Thr436Ala missense_variant 12/181 ENSP00000257897 A1Q99490-2
AGAP2ENST00000328568.9 linkuse as main transcriptc.1906A>G p.Thr636Ala missense_variant 12/185 ENSP00000328160
AGAP2ENST00000549129.1 linkuse as main transcriptc.382A>G p.Thr128Ala missense_variant 5/53 ENSP00000446683

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152210
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.000118
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000200
AC:
5
AN:
250160
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135320
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000545
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:
0.0000555
AC:
81
AN:
1460750
Hom.:
0
Cov.:
30
AF XY:
0.0000564
AC XY:
41
AN XY:
726688
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000657
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.0000657
AC:
10
AN:
152210
Hom.:
0
Cov.:
33
AF XY:
0.0000672
AC XY:
5
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000116
Hom.:
0
Bravo
AF:
0.0000756
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.0000330
AC:
4

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 submitterclinical testingAmbry GeneticsFeb 22, 2023The c.2314A>G (p.T772A) alteration is located in exon 12 (coding exon 12) of the AGAP2 gene. This alteration results from a A to G substitution at nucleotide position 2314, causing the threonine (T) at amino acid position 772 to be replaced by an alanine (A). 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
-0.17
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
16
DANN
Benign
0.62
DEOGEN2
Benign
0.014
.;.;T
Eigen
Benign
-0.81
Eigen_PC
Benign
-0.69
FATHMM_MKL
Benign
0.36
N
LIST_S2
Benign
0.61
T;T;T
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.088
T;T;T
MetaSVM
Benign
-0.99
T
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-0.10
N;N;N
REVEL
Benign
0.15
Sift
Benign
0.55
T;T;T
Sift4G
Benign
0.73
T;T;T
Polyphen
0.0010
B;B;.
Vest4
0.38
MVP
0.58
MPC
0.51
ClinPred
0.075
T
GERP RS
0.75
gMVP
0.30

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.

Other links and lift over

dbSNP: rs374744170; hg19: chr12-58124392; API