chr12-57729733-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_001122772.3(AGAP2):ā€‹c.2463T>Cā€‹(p.Ser821=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000141 in 1,613,474 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: š‘“ 0.00072 ( 3 hom., cov: 31)
Exomes š‘“: 0.000080 ( 1 hom. )

Consequence

AGAP2
NM_001122772.3 synonymous

Scores

2

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.12
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]

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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=-0.57).
BP6
Variant 12-57729733-A-G is Benign according to our data. Variant chr12-57729733-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3058107.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=2.12 with no splicing effect.
BS2
High AC in GnomAd4 at 110 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
AGAP2NM_001122772.3 linkuse as main transcriptc.2463T>C p.Ser821= synonymous_variant 13/19 ENST00000547588.6 NP_001116244.1
AGAP2NM_014770.4 linkuse as main transcriptc.1455T>C p.Ser485= synonymous_variant 13/18 NP_055585.1
AGAP2XM_005268625.4 linkuse as main transcriptc.2463T>C p.Ser821= synonymous_variant 13/18 XP_005268682.1
AGAP2XM_005268626.3 linkuse as main transcriptc.1455T>C p.Ser485= synonymous_variant 13/19 XP_005268683.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
AGAP2ENST00000547588.6 linkuse as main transcriptc.2463T>C p.Ser821= synonymous_variant 13/191 NM_001122772.3 ENSP00000449241 P3
AGAP2ENST00000257897.7 linkuse as main transcriptc.1455T>C p.Ser485= synonymous_variant 13/181 ENSP00000257897 A1Q99490-2
AGAP2ENST00000328568.9 linkuse as main transcriptc.2055T>C p.Ser685= synonymous_variant 13/185 ENSP00000328160

Frequencies

GnomAD3 genomes
AF:
0.000678
AC:
103
AN:
152014
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00230
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000328
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000962
GnomAD3 exomes
AF:
0.000187
AC:
47
AN:
250828
Hom.:
0
AF XY:
0.000170
AC XY:
23
AN XY:
135586
show subpopulations
Gnomad AFR exome
AF:
0.00247
Gnomad AMR exome
AF:
0.000203
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000801
AC:
117
AN:
1461342
Hom.:
1
Cov.:
30
AF XY:
0.0000688
AC XY:
50
AN XY:
726992
show subpopulations
Gnomad4 AFR exome
AF:
0.00269
Gnomad4 AMR exome
AF:
0.000179
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.000265
GnomAD4 genome
AF:
0.000723
AC:
110
AN:
152132
Hom.:
3
Cov.:
31
AF XY:
0.000834
AC XY:
62
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.00248
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000952
Alfa
AF:
0.000483
Hom.:
0
Bravo
AF:
0.000820
Asia WGS
AF:
0.00144
AC:
5
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

AGAP2-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesMar 25, 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
8.1
DANN
Benign
0.84

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: rs149262637; hg19: chr12-58123516; API