rs12368653

Variant names:

• chr12-57739473-G-A
• rs12368653
• ENST00000257897.7:c.160+2439C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-57739473-G-A
• chr12-57739473-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014770.4(AGAP2):​c.160+2439C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 151,960 control chromosomes in the GnomAD database, including 13,064 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 0.40 (13064 hom., cov: 31)
• Consequence: AGAP2 NM_014770.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.390
• Publications: 86 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]

TSPAN31 (HGNC:10539): (tetraspanin 31) The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is thought to be involved in growth-related cellular processes. This gene is associated with tumorigenesis and osteosarcoma. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.485 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.160+2439C>T		intron	N/A	NP_055585.1	Q99490-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGAP2	ENST00000257897.7	TSL:1	c.160+2439C>T		intron	N/A	ENSP00000257897.3	Q99490-2
	TSPAN31	ENST00000553221.5	TSL:3	n.189+1272G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60486 AN: 151842 Hom.: 13072 Cov.: 31

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.481

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

GnomAD4 genome AF: 0.398 AC: 60475 AN: 151960 Hom.: 13064 Cov.: 31 AF XY: 0.393 AC XY: 29167 AN XY: 74224

African (AFR) AF: 0.274 AC: 11342 AN: 41418

American (AMR) AF: 0.376 AC: 5754 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 2012 AN: 3472

East Asian (EAS) AF: 0.164 AC: 848 AN: 5174

South Asian (SAS) AF: 0.281 AC: 1354 AN: 4814

European-Finnish (FIN) AF: 0.417 AC: 4395 AN: 10542

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.490 AC: 33276 AN: 67942

Other (OTH) AF: 0.477 AC: 1005 AN: 2106

Alfa AF: 0.453 Hom.: 49477

Bravo AF: 0.387

Asia WGS AF: 0.244 AC: 851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.4
DANN	Benign	0.77
PhyloP100		0.39
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12368653; hg19: chr12-58133256;