Variant 12-57729675-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001122772.3(AGAP2):c.2521C>G(p.Pro841Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,502 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

AGAP2
NM_001122772.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.66

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16501051).

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGAP2	NM_001122772.3 link	c.2521C>G	p.Pro841Ala	missense_variant	Exon 13 of 19	ENST00000547588.6	NP_001116244.1	Q99490F8VVT9
AGAP2	NM_014770.4 link	c.1513C>G	p.Pro505Ala	missense_variant	Exon 13 of 18		NP_055585.1	Q99490-2A0A024RB55
AGAP2	XM_005268625.4 link	c.2521C>G	p.Pro841Ala	missense_variant	Exon 13 of 18		XP_005268682.1
AGAP2	XM_005268626.3 link	c.1513C>G	p.Pro505Ala	missense_variant	Exon 13 of 19		XP_005268683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AGAP2	ENST00000547588.6 link	c.2521C>G	p.Pro841Ala	missense_variant	Exon 13 of 19	1	NM_001122772.3	ENSP00000449241.1	F8VVT9
AGAP2	ENST00000257897.7 link	c.1513C>G	p.Pro505Ala	missense_variant	Exon 13 of 18	1		ENSP00000257897.3	Q99490-2
AGAP2	ENST00000328568.9 link	c.2110C>G	p.Pro704Ala	missense_variant	Exon 13 of 18	5		ENSP00000328160.4	J3KNM6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251162

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135746

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461502

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727044

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2024

The c.2521C>G (p.P841A) alteration is located in exon 13 (coding exon 13) of the AGAP2 gene. This alteration results from a C to G substitution at nucleotide position 2521, causing the proline (P) at amino acid position 841 to be replaced by an alanine (A). 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

-0.12

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.78

Eigen

Benign

-0.095

Eigen_PC

Benign

0.025

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.80

N;N

REVEL

Benign

0.084

Sift

Benign

0.52

T;T

Sift4G

Benign

0.82

T;T

Polyphen

0.56

P;D

Vest4

0.31

MutPred

0.27

.;Loss of sheet (P = 0.0228);

MVP

0.36

MPC

1.2

ClinPred

0.31

GERP RS

4.4

gMVP

0.22

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over