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GeneBe

12-57730577-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001122772.3(AGAP2):c.2346C>T(p.Pro782=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000366 in 1,614,132 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

AGAP2
NM_001122772.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.750
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 Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-57730577-G-A is Benign according to our data. Variant chr12-57730577-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3039943.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.75 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 294 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AGAP2NM_001122772.3 linkuse as main transcriptc.2346C>T p.Pro782= synonymous_variant 12/19 ENST00000547588.6
AGAP2NM_014770.4 linkuse as main transcriptc.1338C>T p.Pro446= synonymous_variant 12/18
AGAP2XM_005268625.4 linkuse as main transcriptc.2346C>T p.Pro782= synonymous_variant 12/18
AGAP2XM_005268626.3 linkuse as main transcriptc.1338C>T p.Pro446= synonymous_variant 12/19

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AGAP2ENST00000547588.6 linkuse as main transcriptc.2346C>T p.Pro782= synonymous_variant 12/191 NM_001122772.3 P3
AGAP2ENST00000257897.7 linkuse as main transcriptc.1338C>T p.Pro446= synonymous_variant 12/181 A1Q99490-2
AGAP2ENST00000328568.9 linkuse as main transcriptc.1938C>T p.Pro646= synonymous_variant 12/185
AGAP2ENST00000549129.1 linkuse as main transcriptc.414C>T p.Pro138= synonymous_variant 5/53

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00193
AC:
294
AN:
152212
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00675
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000720
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:
0.000956
GnomAD3 exomes
AF:
0.000394
AC:
99
AN:
251346
Hom.:
0
AF XY:
0.000302
AC XY:
41
AN XY:
135848
show subpopulations
Gnomad AFR exome
AF:
0.00578
Gnomad AMR exome
AF:
0.0000868
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000202
AC:
295
AN:
1461802
Hom.:
0
Cov.:
30
AF XY:
0.000165
AC XY:
120
AN XY:
727192
show subpopulations
Gnomad4 AFR exome
AF:
0.00753
Gnomad4 AMR exome
AF:
0.000134
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.000497
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00194
AC:
296
AN:
152330
Hom.:
1
Cov.:
33
AF XY:
0.00196
AC XY:
146
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.00678
Gnomad4 AMR
AF:
0.000719
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:
0.000946
Alfa
AF:
0.000171
Hom.:
0
Bravo
AF:
0.00213
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

AGAP2-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 28, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.57
Cadd
Benign
8.2
Dann
Benign
0.79

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: rs148450672; hg19: chr12-58124360; API