12-57729714-G-A

Position:

• chr12-57729714-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001122772.3(AGAP2):​c.2482C>T​(p.Pro828Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: AGAP2 NM_001122772.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.14

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28568172).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGAP2	NM_001122772.3	c.2482C>T	p.Pro828Ser	missense_variant	Exon 13 of 19	ENST00000547588.6	NP_001116244.1
AGAP2	NM_014770.4	c.1474C>T	p.Pro492Ser	missense_variant	Exon 13 of 18		NP_055585.1
AGAP2	XM_005268625.4	c.2482C>T	p.Pro828Ser	missense_variant	Exon 13 of 18		XP_005268682.1
AGAP2	XM_005268626.3	c.1474C>T	p.Pro492Ser	missense_variant	Exon 13 of 19		XP_005268683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGAP2	ENST00000547588.6	c.2482C>T	p.Pro828Ser	missense_variant	Exon 13 of 19	1	NM_001122772.3	ENSP00000449241.1
AGAP2	ENST00000257897.7	c.1474C>T	p.Pro492Ser	missense_variant	Exon 13 of 18	1		ENSP00000257897.3
AGAP2	ENST00000328568.9	c.2071C>T	p.Pro691Ser	missense_variant	Exon 13 of 18	5		ENSP00000328160.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 02, 2024

The c.2482C>T (p.P828S) alteration is located in exon 13 (coding exon 13) of the AGAP2 gene. This alteration results from a C to T substitution at nucleotide position 2482, causing the proline (P) at amino acid position 828 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	25
DANN	Uncertain	1.0
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.86	T
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-3.1	D;D
REVEL	Benign	0.14
Sift	Benign	0.066	T;T
Sift4G	Benign	0.11	T;T
Polyphen		0.91	P;B
Vest4		0.54
MutPred		0.34		.;Gain of phosphorylation at P828 (P = 0.0037);
MVP		0.43
MPC		1.4
ClinPred		0.98	D
GERP RS		4.4
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-58123497;