11-65014251-G-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP5BP4BS2_Supporting

The NM_001667.4(ARL2):​c.44G>T​(p.Arg15Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000324 in 1,574,732 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 Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

ARL2
NM_001667.4 missense

Scores

3
11
5

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 8.86
Variant links:
Genes affected
ARL2 (HGNC:693): (ADP ribosylation factor like GTPase 2) This gene encodes a small GTP-binding protein of the RAS superfamily which functions as an ADP-ribosylation factor (ARF). The encoded protein is one of a functionally distinct group of ARF-like genes. [provided by RefSeq, Jul 2008]
ARL2-SNX15 (HGNC:49197): (ARL2-SNX15 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring ADP-ribosylation factor-like 2 (ARL2) and sorting nexin 15 (SNX15) genes on chromosome 11. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is therefore unlikely to produce a protein product. [provided by RefSeq, Dec 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PP5
Variant 11-65014251-G-T is Pathogenic according to our data. Variant chr11-65014251-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 983502.Status of the report is no_assertion_criteria_provided, 0 stars.
BP4
Computational evidence support a benign effect (MetaRNN=0.15557343). . Strength limited to SUPPORTING due to the PP5.
BS2
High AC in GnomAd4 at 9 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ARL2NM_001667.4 linkuse as main transcriptc.44G>T p.Arg15Leu missense_variant 1/5 ENST00000246747.9 NP_001658.2 P36404-1Q53YD8
ARL2NM_001199745.2 linkuse as main transcriptc.44G>T p.Arg15Leu missense_variant 1/4 NP_001186674.1 P36404-2
ARL2-SNX15NR_037650.2 linkuse as main transcriptn.92G>T non_coding_transcript_exon_variant 1/11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ARL2ENST00000246747.9 linkuse as main transcriptc.44G>T p.Arg15Leu missense_variant 1/51 NM_001667.4 ENSP00000246747.4 P36404-1
ARL2-SNX15ENST00000301886.3 linkuse as main transcriptn.44G>T non_coding_transcript_exon_variant 1/112 ENSP00000476630.1 V9GYD0

Frequencies

GnomAD3 genomes
AF:
0.0000591
AC:
9
AN:
152172
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00154
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000841
AC:
17
AN:
202158
Hom.:
0
AF XY:
0.0000717
AC XY:
8
AN XY:
111500
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00115
Gnomad SAS exome
AF:
0.0000785
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000108
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000295
AC:
42
AN:
1422442
Hom.:
0
Cov.:
30
AF XY:
0.0000269
AC XY:
19
AN XY:
707016
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000997
Gnomad4 SAS exome
AF:
0.0000490
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000274
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000591
AC:
9
AN:
152290
Hom.:
0
Cov.:
32
AF XY:
0.0000537
AC XY:
4
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00155
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000680
Hom.:
0
Bravo
AF:
0.0000718
ExAC
AF:
0.0000913
AC:
11

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Microcornea, rod-cone dystrophy, cataract, and posterior staphyloma 1 Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMOct 13, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.68
BayesDel_addAF
Benign
-0.089
T
BayesDel_noAF
Uncertain
0.050
CADD
Pathogenic
32
DANN
Uncertain
1.0
DEOGEN2
Benign
0.15
T;T;.
Eigen
Uncertain
0.45
Eigen_PC
Uncertain
0.53
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Uncertain
0.93
.;D;D
M_CAP
Uncertain
0.12
D
MetaRNN
Benign
0.16
T;T;T
MetaSVM
Benign
-0.47
T
MutationAssessor
Uncertain
2.6
M;M;M
PrimateAI
Pathogenic
0.86
D
PROVEAN
Pathogenic
-4.4
D;D;D
REVEL
Uncertain
0.43
Sift
Uncertain
0.0080
D;D;D
Sift4G
Uncertain
0.0090
D;D;D
Polyphen
0.11
B;B;.
Vest4
0.69
MVP
0.64
MPC
0.37
ClinPred
0.46
T
GERP RS
4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.75
gMVP
0.77

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.

Other links and lift over

dbSNP: rs184873330; hg19: chr11-64781723; API