Genetic Variant AGAP2:c.2308+40G>C (chr12-57730751-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001122772.3(AGAP2):c.2308+40G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 1,611,768 control chromosomes in the GnomAD database, including 82,982 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.24 ( 5501 hom., cov: 33)

Exomes 𝑓: 0.31 ( 77481 hom. )

Consequence

AGAP2
NM_001122772.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.86

Publications

18 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001122772.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGAP2	NM_001122772.3	MANE Select	c.2308+40G>C		intron	N/A	NP_001116244.1
	AGAP2	NM_014770.4		c.1300+40G>C		intron	N/A	NP_055585.1	Q99490-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AGAP2	ENST00000547588.6	TSL:1 MANE Select	c.2308+40G>C	intron	N/A	ENSP00000449241.1
AGAP2	ENST00000257897.7	TSL:1	c.1300+40G>C	intron	N/A	ENSP00000257897.3	Q99490-2
AGAP2	ENST00000943666.1		c.2308+40G>C	intron	N/A	ENSP00000613725.1

Frequencies

GnomAD3 genomes

AF:

0.237

AC:

35997

AN:

152014

Hom.:

5498

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0638

Gnomad AMI

AF:

0.334

Gnomad AMR

AF:

0.180

Gnomad ASJ

AF:

0.190

Gnomad EAS

AF:

0.506

Gnomad SAS

AF:

0.455

Gnomad FIN

AF:

0.369

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.301

Gnomad OTH

AF:

0.213

GnomAD2 exomes

AF:

0.304

AC:

75554

AN:

248848

AF XY:

0.316

show subpopulations

Gnomad AFR exome

AF:

0.0584

Gnomad AMR exome

AF:

0.191

Gnomad ASJ exome

AF:

0.192

Gnomad EAS exome

AF:

0.498

Gnomad FIN exome

AF:

0.355

Gnomad NFE exome

AF:

0.302

Gnomad OTH exome

AF:

0.265

GnomAD4 exome

AF:

0.315

AC:

459722

AN:

1459636

Hom.:

77481

Cov.:

AF XY:

0.319

AC XY:

231640

AN XY:

726120

show subpopulations

African (AFR)

AF:

0.0531

AC:

1776

AN:

33438

American (AMR)

AF:

0.191

AC:

8524

AN:

44546

Ashkenazi Jewish (ASJ)

AF:

0.195

AC:

5090

AN:

26112

East Asian (EAS)

AF:

0.595

AC:

23616

AN:

39692

South Asian (SAS)

AF:

0.447

AC:

38542

AN:

86142

European-Finnish (FIN)

AF:

0.347

AC:

18260

AN:

52692

Middle Eastern (MID)

AF:

0.160

AC:

815

AN:

5086

European-Non Finnish (NFE)

AF:

0.311

AC:

345444

AN:

1111664

Other (OTH)

AF:

0.293

AC:

17655

AN:

60264

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

18672

37343

56015

74686

93358

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11396

22792

34188

45584

56980

<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:

0.237

AC:

35997

AN:

152132

Hom.:

5501

Cov.:

AF XY:

0.243

AC XY:

18052

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.0635

AC:

2640

AN:

41548

American (AMR)

AF:

0.180

AC:

2754

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.190

AC:

661

AN:

3470

East Asian (EAS)

AF:

0.506

AC:

2612

AN:

5162

South Asian (SAS)

AF:

0.456

AC:

2197

AN:

4814

European-Finnish (FIN)

AF:

0.369

AC:

3896

AN:

10570

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.301

AC:

20462

AN:

67960

Other (OTH)

AF:

0.210

AC:

443

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1315

2629

3944

5258

6573

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

398

796

1194

1592

1990

<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:

0.189

Hom.:

628

Bravo

AF:

0.210

Asia WGS

AF:

0.412

AC:

1432

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

(source)

DANN

Benign

0.45

PhyloP100

1.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over