chr12-57741915-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_014770.4(AGAP2):​c.157C>T​(p.Arg53*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000151 in 1,613,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

AGAP2
NM_014770.4 stop_gained

Scores

1
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.12
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]
TSPAN31 (HGNC:10539): (tetraspanin 31) The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is thought to be involved in growth-related cellular processes. This gene is associated with tumorigenesis and osteosarcoma. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AGAP2NM_014770.4 linkc.157C>T p.Arg53* stop_gained Exon 1 of 18 NP_055585.1 Q99490-2A0A024RB55
AGAP2XM_005268626.3 linkc.157C>T p.Arg53* stop_gained Exon 1 of 19 XP_005268683.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AGAP2ENST00000257897.7 linkc.157C>T p.Arg53* stop_gained Exon 1 of 18 1 ENSP00000257897.3 Q99490-2
TSPAN31ENST00000547311.5 linkn.235+1945G>A intron_variant Intron 1 of 2 3
TSPAN31ENST00000550528.5 linkn.105+1945G>A intron_variant Intron 1 of 2 3
TSPAN31ENST00000553221.5 linkn.190-1325G>A intron_variant Intron 1 of 5 3

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152158
Hom.:
0
Cov.:
32
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:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000283
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000518
AC:
13
AN:
250968
Hom.:
0
AF XY:
0.0000590
AC XY:
8
AN XY:
135644
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000115
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000159
AC:
233
AN:
1461010
Hom.:
0
Cov.:
33
AF XY:
0.000160
AC XY:
116
AN XY:
726678
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000936
Gnomad4 NFE exome
AF:
0.000199
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.0000657
AC:
10
AN:
152158
Hom.:
0
Cov.:
32
AF XY:
0.000108
AC XY:
8
AN XY:
74322
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000283
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000106
Hom.:
0
Bravo
AF:
0.0000453
TwinsUK
AF:
0.000539
AC:
2
ALSPAC
AF:
0.000778
AC:
3
ExAC
AF:
0.0000824
AC:
10
EpiCase
AF:
0.000164
EpiControl
AF:
0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.56
T
BayesDel_noAF
Benign
-0.81
CADD
Benign
13
DANN
Uncertain
1.0
Eigen
Benign
-0.20
Eigen_PC
Benign
-0.26
FATHMM_MKL
Benign
0.64
D
Vest4
0.35
GERP RS
3.0

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: rs143760313; hg19: chr12-58135698; COSMIC: COSV57727143; COSMIC: COSV57727143; API