12-57730751-C-G

Position:

• chr12-57730751-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGAP2	NM_001122772.3	c.2308+40G>C		intron_variant		ENST00000547588.6	NP_001116244.1
AGAP2	NM_014770.4	c.1300+40G>C		intron_variant			NP_055585.1
AGAP2	XM_005268625.4	c.2308+40G>C		intron_variant			XP_005268682.1
AGAP2	XM_005268626.3	c.1300+40G>C		intron_variant			XP_005268683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGAP2	ENST00000547588.6	c.2308+40G>C		intron_variant		1	NM_001122772.3	ENSP00000449241.1
AGAP2	ENST00000257897.7	c.1300+40G>C		intron_variant		1		ENSP00000257897.3
AGAP2	ENST00000328568.9	c.1897+40G>C		intron_variant		5		ENSP00000328160.4
AGAP2	ENST00000549129.1	c.376+40G>C		intron_variant		3		ENSP00000446683.1

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35997 AN: 152014 Hom.: 5498 Cov.: 33

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

GnomAD3 exomes AF: 0.304 AC: 75554 AN: 248848 Hom.: 13227 AF XY: 0.316 AC XY: 42621 AN XY: 134706

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 SAS exome AF: 0.456

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.: 37 AF XY: 0.319 AC XY: 231640 AN XY: 726120

Gnomad4 AFR exome AF: 0.0531

Gnomad4 AMR exome AF: 0.191

Gnomad4 ASJ exome AF: 0.195

Gnomad4 EAS exome AF: 0.595

Gnomad4 SAS exome AF: 0.447

Gnomad4 FIN exome AF: 0.347

Gnomad4 NFE exome AF: 0.311

Gnomad4 OTH exome AF: 0.293

GnomAD4 genome AF: 0.237 AC: 35997 AN: 152132 Hom.: 5501 Cov.: 33 AF XY: 0.243 AC XY: 18052 AN XY: 74370

Gnomad4 AFR AF: 0.0635

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.506

Gnomad4 SAS AF: 0.456

Gnomad4 FIN AF: 0.369

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.210

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.45

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

LitVar

Other links and lift over

dbSNP: rs2301551; hg19: chr12-58124534; COSMIC: COSV57733485; COSMIC: COSV57733485;