rs1015516060

Variant names:

• chr12-57726761-C-G
• rs1015516060
• NM_001122772.3:c.3370G>C

Your query was ambiguous. Multiple possible variants found:

• chr12-57726761-C-G
• chr12-57726761-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001122772.3(AGAP2):​c.3370G>C​(p.Gly1124Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1124S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AGAP2 NM_001122772.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.76
• Publications: 0 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]

AGAP2-AS1 (HGNC:48633): (AGAP2 antisense RNA 1) Biomarker of lung non-small cell carcinoma; malignant astrocytoma; and stomach cancer. [provided by Alliance of Genome Resources, Apr 2022]

OS9 (HGNC:16994): (OS9 endoplasmic reticulum lectin) This gene encodes a protein that is highly expressed in osteosarcomas. This protein binds to the hypoxia-inducible factor 1 (HIF-1), a key regulator of the hypoxic response and angiogenesis, and promotes the degradation of one of its subunits. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.866

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGAP2	NM_001122772.3	c.3370G>C	p.Gly1124Arg	missense_variant	Exon 19 of 19	ENST00000547588.6	NP_001116244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGAP2	ENST00000547588.6	c.3370G>C	p.Gly1124Arg	missense_variant	Exon 19 of 19	1	NM_001122772.3	ENSP00000449241.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1203428 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 580140

African (AFR) AF: 0.00 AC: 0 AN: 23246

American (AMR) AF: 0.00 AC: 0 AN: 11342

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16266

East Asian (EAS) AF: 0.00 AC: 0 AN: 27446

South Asian (SAS) AF: 0.00 AC: 0 AN: 52564

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29278

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3822

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 990426

Other (OTH) AF: 0.00 AC: 0 AN: 49038

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	29
DANN	Uncertain	1.0
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Pathogenic	0.88	D
MetaRNN	Pathogenic	0.87	D;D
MetaSVM	Uncertain	0.066	D
PhyloP100		4.8
PrimateAI	Pathogenic	0.91	D
PROVEAN	Pathogenic	-6.3	D;D
REVEL	Pathogenic	0.73
Sift	Uncertain	0.0010	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		0.87	P;P
Vest4		0.64
MutPred		0.62		.;Gain of MoRF binding (P = 0.0214);
MVP		0.83
MPC		2.6
ClinPred		1.0	D
GERP RS		3.3
gMVP		0.88
Mutation Taster		=38/62	disease causing

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: rs1015516060; hg19: chr12-58120544;