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 NM_014770.4(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
NM_014770.4 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:

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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=-0.81).

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014770.4. 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_014770.4		c.*2690A>G		3_prime_UTR	Exon 18 of 18	NP_055585.1	Q99490-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGAP2	ENST00000257897.7	TSL:1	c.*2690A>G		3_prime_UTR	Exon 18 of 18	ENSP00000257897.3	Q99490-2
	OS9	ENST00000700670.1		c.286+2994T>C		intron	N/A	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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over