rs7198865

Positions:

chr16-57249818-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_012106.4(ARL2BP):c.259G>A(p.Glu87Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0283 in 1,614,112 control chromosomes in the GnomAD database, including 826 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.020 ( 46 hom., cov: 32)

Exomes 𝑓: 0.029 ( 780 hom. )

Consequence

ARL2BP
NM_012106.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 6.05

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:

LOC124903697 (HGNC:):

LOC124903697 links:

PLLP (HGNC:18553): (plasmolipin) Predicted to be a structural constituent of myelin sheath. Predicted to be involved in myelination. Predicted to be located in compact myelin and membrane raft. Predicted to be integral component of membrane. Biomarker of schizophrenia. [provided by Alliance of Genome Resources, Apr 2022]

PLLP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035790205).

BP6

Variant 16-57249818-G-A is Benign according to our data. Variant chr16-57249818-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 402395.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.02 (3039/152328) while in subpopulation NFE AF= 0.0311 (2114/68028). AF 95% confidence interval is 0.03. There are 46 homozygotes in gnomad4. There are 1342 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 46 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ARL2BP	NM_012106.4 linkuse as main transcript	c.259G>A	p.Glu87Lys	missense_variant	4/6	ENST00000219204.8	NP_036238.1
LOC124903697	XR_007065082.1 linkuse as main transcript	n.243C>T		non_coding_transcript_exon_variant	2/2
ARL2BP	XM_047433883.1 linkuse as main transcript	c.163G>A	p.Glu55Lys	missense_variant	4/6		XP_047289839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARL2BP	ENST00000219204.8 linkuse as main transcript	c.259G>A	p.Glu87Lys	missense_variant	4/6	1	NM_012106.4	ENSP00000219204	P1	Q9Y2Y0-1

Frequencies

GnomAD3 genomes

AF:

0.0200

AC:

3038

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00702

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0200

Gnomad ASJ

AF:

0.0671

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00320

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0311

Gnomad OTH

AF:

0.0196

GnomAD3 exomes

AF:

0.0204

AC:

5130

AN:

251464

Hom.:

AF XY:

0.0203

AC XY:

2759

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.00732

Gnomad AMR exome

AF:

0.0160

Gnomad ASJ exome

AF:

0.0659

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00438

Gnomad FIN exome

AF:

0.00309

Gnomad NFE exome

AF:

0.0302

Gnomad OTH exome

AF:

0.0262

GnomAD4 exome

AF:

0.0291

AC:

42606

AN:

1461784

Hom.:

780

Cov.:

AF XY:

0.0284

AC XY:

20622

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.00618

Gnomad4 AMR exome

AF:

0.0173

Gnomad4 ASJ exome

AF:

0.0656

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00466

Gnomad4 FIN exome

AF:

0.00417

Gnomad4 NFE exome

AF:

0.0339

Gnomad4 OTH exome

AF:

0.0251

GnomAD4 genome

AF:

0.0200

AC:

3039

AN:

152328

Hom.:

Cov.:

AF XY:

0.0180

AC XY:

1342

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00700

Gnomad4 AMR

AF:

0.0200

Gnomad4 ASJ

AF:

0.0671

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00248

Gnomad4 FIN

AF:

0.00320

Gnomad4 NFE

AF:

0.0311

Gnomad4 OTH

AF:

0.0194

Alfa

AF:

0.0313

Hom.:

198

Bravo

AF:

0.0220

TwinsUK

AF:

0.0326

AC:

121

ALSPAC

AF:

0.0376

AC:

145

ESP6500AA

AF:

0.00773

AC:

ESP6500EA

AF:

0.0352

AC:

303

ExAC

AF:

0.0196

AC:

2382

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.0305

EpiControl

AF:

0.0350

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency, I think this gene may cause ciliopathy, but probably not PCD specifically -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.044

T;.

Eigen

Benign

-0.074

Eigen_PC

Benign

0.14

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.50

T;T

MetaRNN

Benign

0.0036

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.71

PROVEAN

Benign

0.050

N;N

REVEL

Benign

0.12

Sift

Benign

0.19

T;T

Sift4G

Benign

0.48

T;T

Polyphen

0.0

B;.

Vest4

0.13

MPC

0.54

ClinPred

0.015

GERP RS

5.8

Varity_R

0.19

gMVP

0.65

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