12-57742040-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_014770.4(AGAP2):c.32C>T(p.Ala11Val) variant causes a missense change. The variant allele was found at a frequency of 0.000605 in 1,614,088 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00064 ( 11 hom. )

Consequence

AGAP2
NM_014770.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 7.00

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]

AGAP2 links:

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]

TSPAN31 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009385824).

BP6

Variant 12-57742040-G-A is Benign according to our data. Variant chr12-57742040-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3052503.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 41 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGAP2	NM_014770.4 link	c.32C>T	p.Ala11Val	missense_variant	Exon 1 of 18		NP_055585.1	Q99490-2A0A024RB55
AGAP2	XM_005268626.3 link	c.32C>T	p.Ala11Val	missense_variant	Exon 1 of 19		XP_005268683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
AGAP2	ENST00000257897.7 link	c.32C>T	p.Ala11Val	missense_variant	Exon 1 of 18	1	ENSP00000257897.3	Q99490-2
TSPAN31	ENST00000547311.5 link	n.235+2070G>A		intron_variant	Intron 1 of 2	3
TSPAN31	ENST00000550528.5 link	n.105+2070G>A		intron_variant	Intron 1 of 2	3
TSPAN31	ENST00000553221.5 link	n.190-1200G>A		intron_variant	Intron 1 of 5	3

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00435

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000819

AC:

206

AN:

251438

AF XY:

0.00124

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000308

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000640

AC:

936

AN:

1461842

Hom.:

Cov.:

AF XY:

0.000840

AC XY:

611

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

AC:

AN:

33480

Gnomad4 AMR exome

AF:

0.0000224

AC:

AN:

44724

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

26136

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39700

Gnomad4 SAS exome

AF:

0.00587

AC:

506

AN:

86258

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

53398

Gnomad4 NFE exome

AF:

0.000371

AC:

412

AN:

1111986

Gnomad4 Remaining exome

AF:

0.000199

AC:

AN:

60392

Heterozygous variant carriers

103

154

206

257

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000269

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.000322

AC XY:

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0000481

AC:

0.0000481487

AN:

0.0000481487

Gnomad4 AMR

AF:

0.0000654

AC:

0.000065368

AN:

0.000065368

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.000193

AC:

0.000193349

AN:

0.000193349

Gnomad4 SAS

AF:

0.00456

AC:

0.00456432

AN:

0.00456432

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000221

AC:

0.000220523

AN:

0.000220523

Gnomad4 OTH

AF:

0.00

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000383

Hom.:

Bravo

AF:

0.000155

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.000848

AC:

103

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000296

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

AGAP2-related disorder

Benign:1

Sep 05, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This 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_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

0.028

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.58

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.0094

MetaSVM

Benign

-1.0

PROVEAN

Benign

-1.4

REVEL

Benign

0.10

Sift

Uncertain

0.0050

Sift4G

Pathogenic

0.0

Polyphen

0.073

Vest4

0.40

MVP

0.59

ClinPred

0.13

GERP RS

4.8

Mutation Taster

=89/11

polymorphism

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over