12-57731844-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001122772.3(AGAP2):c.1918C>T(p.His640Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000277 in 1,445,396 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: not found (cov: 32)
Exomes 𝑓: 0.0000028 ( 0 hom. )
Consequence
AGAP2
NM_001122772.3 missense
NM_001122772.3 missense
Scores
1
6
9
Clinical Significance
Conservation
PhyloP100: 2.83
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]
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ACMG classification
Classification made for transcript
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=0.34189862).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AGAP2 | NM_001122772.3 | c.1918C>T | p.His640Tyr | missense_variant | 8/19 | ENST00000547588.6 | |
AGAP2 | NM_014770.4 | c.910C>T | p.His304Tyr | missense_variant | 8/18 | ||
AGAP2 | XM_005268625.4 | c.1918C>T | p.His640Tyr | missense_variant | 8/18 | ||
AGAP2 | XM_005268626.3 | c.910C>T | p.His304Tyr | missense_variant | 8/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGAP2 | ENST00000547588.6 | c.1918C>T | p.His640Tyr | missense_variant | 8/19 | 1 | NM_001122772.3 | P3 | |
AGAP2 | ENST00000257897.7 | c.910C>T | p.His304Tyr | missense_variant | 8/18 | 1 | A1 | ||
AGAP2 | ENST00000328568.9 | c.1510C>T | p.His504Tyr | missense_variant | 8/18 | 5 | |||
AGAP2 | ENST00000549129.1 | upstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000277 AC: 4AN: 1445396Hom.: 0 Cov.: 33 AF XY: 0.00000418 AC XY: 3AN XY: 717870
GnomAD4 exome
AF:
AC:
4
AN:
1445396
Hom.:
Cov.:
33
AF XY:
AC XY:
3
AN XY:
717870
Gnomad4 AFR exome
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Gnomad4 AMR exome
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Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
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Gnomad4 SAS exome
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Gnomad4 FIN exome
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Gnomad4 OTH exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
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 | Jul 19, 2023 | The c.1918C>T (p.H640Y) alteration is located in exon 8 (coding exon 8) of the AGAP2 gene. This alteration results from a C to T substitution at nucleotide position 1918, causing the histidine (H) at amino acid position 640 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Benign
T;D
Polyphen
D;D
Vest4
MutPred
0.22
.;Gain of phosphorylation at H640 (P = 0.0587);
MVP
MPC
1.5
ClinPred
D
GERP RS
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at