dbSNP rs1293111951: ARL2BP:p.Ala16Thr (chr16-57246087-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_012106.4(ARL2BP):c.46G>A(p.Ala16Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,714 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ARL2BP
NM_012106.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.30

Variant links:

Genes affected

ARL2BP (HGNC:17146): (ADP ribosylation factor like GTPase 2 binding protein) ADP-ribosylation factor (ARF)-like proteins (ARLs) comprise a functionally distinct group of the ARF family of RAS-related GTPases. The protein encoded by this gene binds to ARL2.GTP with high affinity but does not interact with ARL2.GDP, activated ARF, or RHO proteins. The lack of detectable membrane association of this protein or ARL2 upon activation of ARL2 is suggestive of actions distinct from those of the ARFs. This protein is considered to be the first ARL2-specific effector identified, due to its interaction with ARL2.GTP but lack of ARL2 GTPase-activating protein activity. [provided by RefSeq, Jul 2008]

ARL2BP links:

ENSG00000276663 (HGNC:):

ENSG00000276663 links:

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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=0.038701385).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARL2BP	NM_012106.4 link	c.46G>A	p.Ala16Thr	missense_variant	Exon 2 of 6	ENST00000219204.8	NP_036238.1	Q9Y2Y0-1A0A024R6U9
ARL2BP	XM_047433883.1 link	c.-51G>A		5_prime_UTR_variant	Exon 2 of 6		XP_047289839.1
LOC124903697	XR_007065082.1 link	n.3974C>T		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARL2BP	ENST00000219204.8 link	c.46G>A	p.Ala16Thr	missense_variant	Exon 2 of 6	1	NM_012106.4	ENSP00000219204.3		Q9Y2Y0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461714

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.0076

T;.

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.48

T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.039

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.49

N;.

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.56

N;N

REVEL

Benign

0.040

Sift

Benign

0.60

T;T

Sift4G

Benign

0.57

T;T

Polyphen

0.0020

B;.

Vest4

0.10

MutPred

0.20

Gain of glycosylation at A16 (P = 0.0106);Gain of glycosylation at A16 (P = 0.0106);

MVP

0.26

MPC

0.46

ClinPred

0.11

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.066

gMVP

0.27

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over