11-47171510-T-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_032389.6(ARFGAP2):c.857A>T(p.Lys286Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0001 in 1,614,208 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 0.00048 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000061 ( 0 hom. )
Consequence
ARFGAP2
NM_032389.6 missense
NM_032389.6 missense
Scores
1
8
6
Clinical Significance
Conservation
PhyloP100: 7.37
Genes affected
ARFGAP2 (HGNC:13504): (ADP ribosylation factor GTPase activating protein 2) Predicted to enable GTPase activator activity. Predicted to be involved in COPI coating of Golgi vesicle. Located in Golgi apparatus; cytosol; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.05522248).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARFGAP2 | NM_032389.6 | c.857A>T | p.Lys286Met | missense_variant | 10/16 | ENST00000524782.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARFGAP2 | ENST00000524782.6 | c.857A>T | p.Lys286Met | missense_variant | 10/16 | 1 | NM_032389.6 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000480 AC: 73AN: 152196Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
73
AN:
152196
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000143 AC: 36AN: 251486Hom.: 0 AF XY: 0.000132 AC XY: 18AN XY: 135922
GnomAD3 exomes
AF:
AC:
36
AN:
251486
Hom.:
AF XY:
AC XY:
18
AN XY:
135922
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000609 AC: 89AN: 1461894Hom.: 0 Cov.: 31 AF XY: 0.0000495 AC XY: 36AN XY: 727248
GnomAD4 exome
AF:
AC:
89
AN:
1461894
Hom.:
Cov.:
31
AF XY:
AC XY:
36
AN XY:
727248
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000479 AC: 73AN: 152314Hom.: 0 Cov.: 32 AF XY: 0.000497 AC XY: 37AN XY: 74464
GnomAD4 genome
?
AF:
AC:
73
AN:
152314
Hom.:
Cov.:
32
AF XY:
AC XY:
37
AN XY:
74464
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
5
ESP6500EA
AF:
AC:
0
ExAC
?
AF:
AC:
13
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 09, 2021 | The c.857A>T (p.K286M) alteration is located in exon 10 (coding exon 10) of the ARFGAP2 gene. This alteration results from a A to T substitution at nucleotide position 857, causing the lysine (K) at amino acid position 286 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T;T;T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
REVEL
Uncertain
Sift4G
Uncertain
D;D;D;.;.
Polyphen
1.0
.;.;D;.;.
Vest4
MVP
MPC
0.94
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
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