12-57741915-G-T

Variant names:

• chr12-57741915-G-T
• rs143760313
• ENST00000257897.7:c.157C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_014770.4(AGAP2):​c.157C>A​(p.Arg53Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.00301 in 1,613,162 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (18 hom.)
• Consequence: AGAP2 NM_014770.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.12
• Publications: 3 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 12-57741915-G-T is Benign according to our data. Variant chr12-57741915-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2643150.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 274 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGAP2	NM_014770.4	c.157C>A	p.Arg53Arg	synonymous_variant	Exon 1 of 18		NP_055585.1
AGAP2	XM_005268626.3	c.157C>A	p.Arg53Arg	synonymous_variant	Exon 1 of 19		XP_005268683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGAP2	ENST00000257897.7	c.157C>A	p.Arg53Arg	synonymous_variant	Exon 1 of 18	1		ENSP00000257897.3
TSPAN31	ENST00000547311.5	n.235+1945G>T		intron_variant	Intron 1 of 2	3
TSPAN31	ENST00000550528.5	n.105+1945G>T		intron_variant	Intron 1 of 2	3
TSPAN31	ENST00000553221.5	n.190-1325G>T		intron_variant	Intron 1 of 5	3

Frequencies

GnomAD3 genomes AF: 0.00180 AC: 274 AN: 152158 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000628

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00329

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.00140 AC: 351 AN: 250968 AF XY: 0.00129

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.000550

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000231

Gnomad NFE exome AF: 0.00271

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00313 AC: 4579 AN: 1461004 Hom.: 18 Cov.: 33 AF XY: 0.00292 AC XY: 2121 AN XY: 726676

African (AFR) AF: 0.000568 AC: 19 AN: 33468

American (AMR) AF: 0.000447 AC: 20 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.000206 AC: 11 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00381 AC: 4237 AN: 1111286

Other (OTH) AF: 0.00484 AC: 292 AN: 60356

GnomAD4 genome AF: 0.00180 AC: 274 AN: 152158 Hom.: 1 Cov.: 32 AF XY: 0.00144 AC XY: 107 AN XY: 74322

African (AFR) AF: 0.000628 AC: 26 AN: 41424

American (AMR) AF: 0.000654 AC: 10 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00329 AC: 224 AN: 68032

Other (OTH) AF: 0.000956 AC: 2 AN: 2092

Alfa AF: 0.000768 Hom.: 0

Bravo AF: 0.00188

EpiCase AF: 0.00420

EpiControl AF: 0.00219

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

AGAP2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	12
DANN	Benign	0.48
PhyloP100		4.1
PromoterAI		-0.055	Neutral
Mutation Taster		=100/0	polymorphism

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: rs143760313; hg19: chr12-58135698; COSMIC: COSV57727255;