Variant chr11-65018416-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000246747.9(ARL2):c.118G>A(p.Asp40Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,457,636 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: 0.0000027 ( 0 hom. )

Consequence

ARL2
ENST00000246747.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.71

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 links:

ARL2-SNX15 (HGNC:):

ARL2-SNX15 links:

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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=0.28817195).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ARL2	NM_001667.4 linkuse as main transcript	c.118G>A	p.Asp40Asn	missense_variant	2/5	ENST00000246747.9	NP_001658.2
ARL2-SNX15	NR_037650.2 linkuse as main transcript	n.166G>A		non_coding_transcript_exon_variant	2/11
ARL2	NM_001199745.2 linkuse as main transcript	c.118G>A	p.Asp40Asn	missense_variant	2/4		NP_001186674.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARL2	ENST00000246747.9 linkuse as main transcript	c.118G>A	p.Asp40Asn	missense_variant	2/5	1	NM_001667.4	ENSP00000246747	P1	P36404-1
ARL2	ENST00000529384.5 linkuse as main transcript	c.118G>A	p.Asp40Asn	missense_variant	2/6	3		ENSP00000436021	P1	P36404-1
ARL2	ENST00000533729.1 linkuse as main transcript	c.118G>A	p.Asp40Asn	missense_variant	2/4	5		ENSP00000432971		P36404-2
ARL2	ENST00000524585.1 linkuse as main transcript	n.155G>A		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000821

AC:

AN:

243516

Hom.:

AF XY:

0.00000761

AC XY:

AN XY:

131368

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad SAS 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:

0.00000274

AC:

AN:

1457636

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724534

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Oct 05, 2023

The c.118G>A (p.D40N) alteration is located in exon 2 (coding exon 2) of the ARL2 gene. This alteration results from a G to A substitution at nucleotide position 118, causing the aspartic acid (D) at amino acid position 40 to be replaced by an asparagine (N). 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

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;T;.

Eigen

Benign

0.010

Eigen_PC

Benign

0.057

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

.;D;D

M_CAP

Benign

0.024

MetaRNN

Benign

0.29

T;T;T

MetaSVM

Benign

-0.67

MutationAssessor

Benign

1.7

L;L;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-3.5

D;D;D

REVEL

Benign

0.27

Sift

Benign

0.042

D;D;D

Sift4G

Benign

0.12

T;T;T

Polyphen

0.0060

B;B;.

Vest4

0.29

MutPred

0.47

Loss of ubiquitination at K35 (P = 0.1498);Loss of ubiquitination at K35 (P = 0.1498);Loss of ubiquitination at K35 (P = 0.1498);

MVP

0.68

MPC

0.28

ClinPred

0.68

GERP RS

3.7

Varity_R

0.64

gMVP

0.62

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over