ENST00000257897.7:c.160+2439C>T

Variant names:

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

Variant summary

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

The ENST00000257897.7(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 ENST00000257897.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.390

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGAP2	NM_014770.4	c.160+2439C>T		intron_variant	Intron 1 of 17		NP_055585.1
AGAP2	XM_005268626.3	c.160+2439C>T		intron_variant	Intron 1 of 18		XP_005268683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGAP2	ENST00000257897.7	c.160+2439C>T		intron_variant	Intron 1 of 17	1		ENSP00000257897.3
TSPAN31	ENST00000553221.5	n.189+1272G>A		intron_variant	Intron 1 of 5	3

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

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.376

Gnomad4 ASJ AF: 0.579

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.417

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.477

Alfa AF: 0.467 Hom.: 23012

Bravo AF: 0.387

Asia WGS AF: 0.244 AC: 851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.4
DANN	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs12368653; hg19: chr12-58133256;