12-57730751-C-G

Variant names:

• chr12-57730751-C-G
• rs2301551
• NM_001122772.3:c.2308+40G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGAP2	NM_001122772.3	c.2308+40G>C		intron_variant	Intron 11 of 18	ENST00000547588.6	NP_001116244.1
AGAP2	NM_014770.4	c.1300+40G>C		intron_variant	Intron 11 of 17		NP_055585.1
AGAP2	XM_005268625.4	c.2308+40G>C		intron_variant	Intron 11 of 17		XP_005268682.1
AGAP2	XM_005268626.3	c.1300+40G>C		intron_variant	Intron 11 of 18		XP_005268683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGAP2	ENST00000547588.6	c.2308+40G>C		intron_variant	Intron 11 of 18	1	NM_001122772.3	ENSP00000449241.1
AGAP2	ENST00000257897.7	c.1300+40G>C		intron_variant	Intron 11 of 17	1		ENSP00000257897.3
AGAP2	ENST00000328568.9	c.1897+40G>C		intron_variant	Intron 11 of 17	5		ENSP00000328160.4
AGAP2	ENST00000549129.1	c.376+40G>C		intron_variant	Intron 4 of 4	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

GnomAD2 exomes AF: 0.304 AC: 75554 AN: 248848 AF XY: 0.316

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

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

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

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: 27 AN: 294

European-Non Finnish (NFE) AF: 0.301 AC: 20462 AN: 67960

Other (OTH) AF: 0.210 AC: 443 AN: 2114

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
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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