12-57731209-T-G

Position:

• chr12-57731209-T-G

Variant summary

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

The NM_001122772.3(AGAP2):​c.2145+157A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,046 control chromosomes in the GnomAD database, including 7,219 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 0.28 (7219 hom., cov: 32)
• Consequence: AGAP2 NM_001122772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.841

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=-0.59).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGAP2	NM_001122772.3	c.2145+157A>C		intron_variant		ENST00000547588.6	NP_001116244.1
AGAP2	NM_014770.4	c.1137+157A>C		intron_variant			NP_055585.1
AGAP2	XM_005268625.4	c.2145+157A>C		intron_variant			XP_005268682.1
AGAP2	XM_005268626.3	c.1137+157A>C		intron_variant			XP_005268683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGAP2	ENST00000547588.6	c.2145+157A>C		intron_variant		1	NM_001122772.3	ENSP00000449241.1
AGAP2	ENST00000257897.7	c.1137+157A>C		intron_variant		1		ENSP00000257897.3
AGAP2	ENST00000328568.9	c.1734+157A>C		intron_variant		5		ENSP00000328160.4
AGAP2	ENST00000549129.1	c.213+157A>C		intron_variant		3		ENSP00000446683.1

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42245 AN: 151928 Hom.: 7219 Cov.: 32

Gnomad AFR AF: 0.0965

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.632

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.255

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.278 AC: 42248 AN: 152046 Hom.: 7219 Cov.: 32 AF XY: 0.285 AC XY: 21157 AN XY: 74336

Gnomad4 AFR AF: 0.0963

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.631

Gnomad4 SAS AF: 0.499

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.335

Gnomad4 OTH AF: 0.252

Alfa AF: 0.319 Hom.: 10794

Bravo AF: 0.257

Asia WGS AF: 0.495 AC: 1718 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	5.7
DANN	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs10877011; hg19: chr12-58124992;