chr12-57738140-G-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001122772.3(AGAP2):c.107C>A(p.Ala36Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000073 in 1,370,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

AGAP2
NM_001122772.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.757

Publications

0 publications found

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:

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]

TSPAN31 links:

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ACMG classification

Classification was made for transcript

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=0.17838237).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGAP2	NM_001122772.3 link	c.107C>A	p.Ala36Glu	missense_variant	Exon 1 of 19	ENST00000547588.6	NP_001116244.1	Q99490F8VVT9
AGAP2	XM_005268625.4 link	c.107C>A	p.Ala36Glu	missense_variant	Exon 1 of 18		XP_005268682.1
AGAP2	NM_014770.4 link	c.161-2713C>A		intron_variant	Intron 1 of 17		NP_055585.1	Q99490-2A0A024RB55
AGAP2	XM_005268626.3 link	c.161-2713C>A		intron_variant	Intron 1 of 18		XP_005268683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AGAP2	ENST00000547588.6 link	c.107C>A	p.Ala36Glu	missense_variant	Exon 1 of 19	1	NM_001122772.3	ENSP00000449241.1	F8VVT9
AGAP2	ENST00000257897.7 link	c.161-2713C>A		intron_variant	Intron 1 of 17	1		ENSP00000257897.3	Q99490-2
TSPAN31	ENST00000553221.5 link	n.128G>T		non_coding_transcript_exon_variant	Exon 1 of 6	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.30e-7

AC:

AN:

1370190

Hom.:

Cov.:

AF XY:

0.00000148

AC XY:

AN XY:

675842

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29644

American (AMR)

AF:

0.00

AC:

AN:

34516

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24570

East Asian (EAS)

AF:

0.00

AC:

AN:

34436

South Asian (SAS)

AF:

0.00

AC:

AN:

78672

European-Finnish (FIN)

AF:

0.0000300

AC:

AN:

33318

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5632

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1072272

Other (OTH)

AF:

0.00

AC:

AN:

57130

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 03, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.107C>A (p.A36E) alteration is located in exon 1 (coding exon 1) of the AGAP2 gene. This alteration results from a C to A substitution at nucleotide position 107, causing the alanine (A) at amino acid position 36 to be replaced by a glutamic acid (E). 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

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.97

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.53

M_CAP

Pathogenic

0.64

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.0

PhyloP100

0.76

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.030

REVEL

Benign

0.049

Sift

Pathogenic

0.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.24

MutPred

0.22

Gain of loop (P = 0.0045);

MVP

0.43

MPC

3.1

ClinPred

0.23

GERP RS

0.44

PromoterAI

0.032

Neutral

(source)

gMVP

0.25

Mutation Taster

=93/7

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over