NM_001122772.3:c.2822A>G

Variant names:

• chr12-57727716-T-C
• rs1347314682
• NM_001122772.3:c.2822A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001122772.3(AGAP2):​c.2822A>G​(p.Lys941Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign 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. K941M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: AGAP2 NM_001122772.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.28
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1420719).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGAP2	NM_001122772.3	c.2822A>G	p.Lys941Arg	missense_variant	Exon 16 of 19	ENST00000547588.6	NP_001116244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGAP2	ENST00000547588.6	c.2822A>G	p.Lys941Arg	missense_variant	Exon 16 of 19	1	NM_001122772.3	ENSP00000449241.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Benign	0.91
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.34	N
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.1	T
PhyloP100		2.3
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	0.67	N;N
REVEL	Benign	0.16
Sift	Benign	0.94	T;T
Sift4G	Benign	0.88	T;T
Polyphen		0.069	B;B
Vest4		0.13
MVP		0.60
MPC		1.1
ClinPred		0.59	D
GERP RS		4.5
gMVP		0.79
Mutation Taster		=62/38	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: rs1347314682; hg19: chr12-58121499;