12-57738201-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001122772.3(AGAP2):c.46C>T(p.Leu16Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000302 in 1,525,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

AGAP2
NM_001122772.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.58

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.25977492).

BS2

High AC in GnomAdExome4 at 43 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGAP2	NM_001122772.3 link	c.46C>T	p.Leu16Phe	missense_variant	Exon 1 of 19	ENST00000547588.6	NP_001116244.1	Q99490F8VVT9
AGAP2	XM_005268625.4 link	c.46C>T	p.Leu16Phe	missense_variant	Exon 1 of 18		XP_005268682.1
AGAP2	NM_014770.4 link	c.161-2774C>T		intron_variant	Intron 1 of 17		NP_055585.1	Q99490-2A0A024RB55
AGAP2	XM_005268626.3 link	c.161-2774C>T		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.46C>T	p.Leu16Phe	missense_variant	Exon 1 of 19	1	NM_001122772.3	ENSP00000449241.1	F8VVT9
AGAP2	ENST00000257897.7 link	c.161-2774C>T		intron_variant	Intron 1 of 17	1		ENSP00000257897.3	Q99490-2
TSPAN31	ENST00000553221.5 link	n.189G>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 1 of 6	3

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151854

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000824

AC:

AN:

121320

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000234

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000313

AC:

AN:

1373242

Hom.:

Cov.:

AF XY:

0.0000295

AC XY:

AN XY:

677588

show subpopulations

African (AFR)

AF:

0.0000337

AC:

AN:

29662

American (AMR)

AF:

0.0000283

AC:

AN:

35288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24662

East Asian (EAS)

AF:

0.00

AC:

AN:

34560

South Asian (SAS)

AF:

0.00

AC:

AN:

78990

European-Finnish (FIN)

AF:

0.0000300

AC:

AN:

33386

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5652

European-Non Finnish (NFE)

AF:

0.0000373

AC:

AN:

1073702

Other (OTH)

AF:

0.00

AC:

AN:

57340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151854

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74162

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41392

American (AMR)

AF:

0.0000655

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10562

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000295

AC:

AN:

67874

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 12, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.46C>T (p.L16F) alteration is located in exon 1 (coding exon 1) of the AGAP2 gene. This alteration results from a C to T substitution at nucleotide position 46, causing the leucine (L) at amino acid position 16 to be replaced by a phenylalanine (F). 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

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

(source)

DANN

Uncertain

1.0

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.30

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.62

M_CAP

Pathogenic

0.68

MetaRNN

Benign

0.26

MetaSVM

Benign

-1.1

PhyloP100

5.6

PrimateAI

Pathogenic

0.97

PROVEAN

Benign

-0.52

REVEL

Benign

0.060

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.042

Polyphen

0.0020

Vest4

0.22

MutPred

0.33

Gain of sheet (P = 0.0477);

MVP

0.48

MPC

2.8

ClinPred

0.61

GERP RS

2.3

PromoterAI

0.022

Neutral

(source)

gMVP

0.66

Mutation Taster

=90/10

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

12-57738201-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over