Genetic Variant AGAP2:c.*2690A>G (chr12-57723862-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000257897.7(AGAP2):c.*2690A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,054 control chromosomes in the GnomAD database, including 8,510 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 0.31 ( 8509 hom., cov: 32)

Exomes 𝑓: 0.38 ( 1 hom. )

Consequence

AGAP2
ENST00000257897.7 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.256

Publications

34 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:

OS9 (HGNC:16994): (OS9 endoplasmic reticulum lectin) This gene encodes a protein that is highly expressed in osteosarcomas. This protein binds to the hypoxia-inducible factor 1 (HIF-1), a key regulator of the hypoxic response and angiogenesis, and promotes the degradation of one of its subunits. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

OS9 links:

Genome browser will be placed here

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=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
AGAP2	NM_014770.4 link	c.*2690A>G	3_prime_UTR_variant	Exon 18 of 18	NP_055585.1	Q99490-2A0A024RB55
AGAP2	XM_005268625.4 link	c.*2690A>G	3_prime_UTR_variant	Exon 18 of 18	XP_005268682.1
AGAP2	XM_005268626.3 link	c.*2690A>G	3_prime_UTR_variant	Exon 19 of 19	XP_005268683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGAP2	ENST00000257897.7 link	c.*2690A>G		3_prime_UTR_variant	Exon 18 of 18	1		ENSP00000257897.3		Q99490-2
OS9	ENST00000700670.1 link	c.286+2994T>C		intron_variant	Intron 3 of 3			ENSP00000515138.1		A0A8V8TQ04

Frequencies

GnomAD3 genomes

AF:

0.308

AC:

46737

AN:

151928

Hom.:

8505

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.386

Gnomad AMR

AF:

0.270

Gnomad ASJ

AF:

0.307

Gnomad EAS

AF:

0.628

Gnomad SAS

AF:

0.538

Gnomad FIN

AF:

0.451

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.364

Gnomad OTH

AF:

0.286

GnomAD4 exome

AF:

0.375

AC:

AN:

Hom.:

Cov.:

AF XY:

0.375

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

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

GnomAD4 genome

AF:

0.308

AC:

46765

AN:

152046

Hom.:

8509

Cov.:

AF XY:

0.316

AC XY:

23468

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.125

AC:

5198

AN:

41500

American (AMR)

AF:

0.270

AC:

4128

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.307

AC:

1065

AN:

3468

East Asian (EAS)

AF:

0.628

AC:

3244

AN:

5166

South Asian (SAS)

AF:

0.538

AC:

2587

AN:

4808

European-Finnish (FIN)

AF:

0.451

AC:

4764

AN:

10552

Middle Eastern (MID)

AF:

0.190

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.364

AC:

24762

AN:

67956

Other (OTH)

AF:

0.289

AC:

610

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1551

3103

4654

6206

7757

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

484

968

1452

1936

2420

<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:

0.337

Hom.:

15641

Bravo

AF:

0.283

Asia WGS

AF:

0.541

AC:

1881

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

9.5

(source)

DANN

Benign

0.89

PhyloP100

-0.26

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over