rs12307841

Positions:

• chr12-57731655-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000547588.6(AGAP2):​c.1954-13A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,613,850 control chromosomes in the GnomAD database, including 13,334 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 0.10 (1104 hom., cov: 32)
  • Exomes 𝑓: 0.12 (12230 hom.)
• Consequence: AGAP2 ENST00000547588.6 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.324

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGAP2	NM_001122772.3	c.1954-13A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000547588.6	NP_001116244.1
AGAP2	NM_014770.4	c.946-13A>G		splice_polypyrimidine_tract_variant, intron_variant			NP_055585.1
AGAP2	XM_005268625.4	c.1954-13A>G		splice_polypyrimidine_tract_variant, intron_variant			XP_005268682.1
AGAP2	XM_005268626.3	c.946-13A>G		splice_polypyrimidine_tract_variant, intron_variant			XP_005268683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGAP2	ENST00000547588.6	c.1954-13A>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001122772.3	ENSP00000449241	P3
AGAP2	ENST00000257897.7	c.946-13A>G		splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000257897	A1
AGAP2	ENST00000328568.9	c.1544-13A>G		splice_polypyrimidine_tract_variant, intron_variant		5		ENSP00000328160
AGAP2	ENST00000549129.1	c.22-13A>G		splice_polypyrimidine_tract_variant, intron_variant		3		ENSP00000446683

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15816 AN: 151982 Hom.: 1101 Cov.: 32

Gnomad AFR AF: 0.0329

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.0603

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.0955

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.0971

GnomAD3 exomes AF: 0.134 AC: 33565 AN: 251238 Hom.: 2906 AF XY: 0.126 AC XY: 17099 AN XY: 135788

Gnomad AFR exome AF: 0.0298

Gnomad AMR exome AF: 0.293

Gnomad ASJ exome AF: 0.0608

Gnomad EAS exome AF: 0.115

Gnomad SAS exome AF: 0.0898

Gnomad FIN exome AF: 0.146

Gnomad NFE exome AF: 0.119

Gnomad OTH exome AF: 0.133

GnomAD4 exome AF: 0.123 AC: 180031 AN: 1461750 Hom.: 12230 Cov.: 34 AF XY: 0.121 AC XY: 87942 AN XY: 727172

Gnomad4 AFR exome AF: 0.0265

Gnomad4 AMR exome AF: 0.282

Gnomad4 ASJ exome AF: 0.0635

Gnomad4 EAS exome AF: 0.0987

Gnomad4 SAS exome AF: 0.0924

Gnomad4 FIN exome AF: 0.146

Gnomad4 NFE exome AF: 0.124

Gnomad4 OTH exome AF: 0.111

GnomAD4 genome AF: 0.104 AC: 15819 AN: 152100 Hom.: 1104 Cov.: 32 AF XY: 0.105 AC XY: 7835 AN XY: 74344

Gnomad4 AFR AF: 0.0328

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.0603

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.0948

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.0961

Alfa AF: 0.115 Hom.: 281

Bravo AF: 0.109

Asia WGS AF: 0.0820 AC: 284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Pathogenic	33
DANN	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.90		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.90		Position offset: -1

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

Publications

LitVar

Other links and lift over

dbSNP: rs12307841; hg19: chr12-58125438; COSMIC: COSV57727342; COSMIC: COSV57727342;