chr12-57741915-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000257897.7(AGAP2):​c.157C>A​(p.Arg53=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00301 in 1,613,162 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0031 ( 18 hom. )

Consequence

AGAP2
ENST00000257897.7 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 12-57741915-G-T is Benign according to our data. Variant chr12-57741915-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2643150.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 274 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
AGAP2NM_014770.4 linkuse as main transcriptc.157C>A p.Arg53= synonymous_variant 1/18 NP_055585.1
AGAP2XM_005268626.3 linkuse as main transcriptc.157C>A p.Arg53= synonymous_variant 1/19 XP_005268683.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
AGAP2ENST00000257897.7 linkuse as main transcriptc.157C>A p.Arg53= synonymous_variant 1/181 ENSP00000257897 A1Q99490-2
TSPAN31ENST00000547311.5 linkuse as main transcriptn.235+1945G>T intron_variant, non_coding_transcript_variant 3
TSPAN31ENST00000550528.5 linkuse as main transcriptn.105+1945G>T intron_variant, non_coding_transcript_variant 3
TSPAN31ENST00000553221.5 linkuse as main transcriptn.190-1325G>T intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.00180
AC:
274
AN:
152158
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000628
Gnomad AMI
AF:
0.0121
Gnomad AMR
AF:
0.000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000943
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00329
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.00140
AC:
351
AN:
250968
Hom.:
0
AF XY:
0.00129
AC XY:
175
AN XY:
135644
show subpopulations
Gnomad AFR exome
AF:
0.000677
Gnomad AMR exome
AF:
0.000550
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000231
Gnomad NFE exome
AF:
0.00271
Gnomad OTH exome
AF:
0.00147
GnomAD4 exome
AF:
0.00313
AC:
4579
AN:
1461004
Hom.:
18
Cov.:
33
AF XY:
0.00292
AC XY:
2121
AN XY:
726676
show subpopulations
Gnomad4 AFR exome
AF:
0.000568
Gnomad4 AMR exome
AF:
0.000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000206
Gnomad4 NFE exome
AF:
0.00381
Gnomad4 OTH exome
AF:
0.00484
GnomAD4 genome
AF:
0.00180
AC:
274
AN:
152158
Hom.:
1
Cov.:
32
AF XY:
0.00144
AC XY:
107
AN XY:
74322
show subpopulations
Gnomad4 AFR
AF:
0.000628
Gnomad4 AMR
AF:
0.000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000943
Gnomad4 NFE
AF:
0.00329
Gnomad4 OTH
AF:
0.000956
Alfa
AF:
0.000775
Hom.:
0
Bravo
AF:
0.00188
EpiCase
AF:
0.00420
EpiControl
AF:
0.00219

ClinVar

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

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJan 01, 2023AGAP2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
12
DANN
Benign
0.48

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: COSV57727255; COSMIC: COSV57727255; API