Variant rs74719094 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018036.7(ATG2B):c.5103A>C(p.Arg1701Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00521 in 1,613,936 control chromosomes in the GnomAD database, including 582 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 85 hom., cov: 32)

Exomes 𝑓: 0.0047 ( 497 hom. )

Consequence

ATG2B
NM_018036.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.541

Variant links:

Genes affected

ATG2B (HGNC:20187): (autophagy related 2B) This gene encodes a protein required for autophagy. The encoded protein is involved in autophagosome formation. A germline duplication of a region that includes this gene is associated with predisposition to myeloid malignancies. [provided by RefSeq, Jul 2016]

ATG2B 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=0.002118796).

BP6

Variant 14-96302043-T-G is Benign according to our data. Variant chr14-96302043-T-G is described in ClinVar as [Benign]. Clinvar id is 1281030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATG2B	NM_018036.7 linkuse as main transcript	c.5103A>C	p.Arg1701Ser	missense_variant	34/42	ENST00000359933.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATG2B	ENST00000359933.6 linkuse as main transcript	c.5103A>C	p.Arg1701Ser	missense_variant	34/42	5	NM_018036.7	P1
ATG2B	ENST00000261834.9 linkuse as main transcript	n.1089A>C		non_coding_transcript_exon_variant	7/14	2

Frequencies

GnomAD3 genomes

AF:

0.0104

AC:

1575

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00198

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0919

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00809

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.0191

GnomAD3 exomes

AF:

0.0201

AC:

5050

AN:

251356

Hom.:

377

AF XY:

0.0151

AC XY:

2056

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.139

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00729

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.0155

GnomAD4 exome

AF:

0.00467

AC:

6828

AN:

1461740

Hom.:

497

Cov.:

AF XY:

0.00391

AC XY:

2842

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.000986

Gnomad4 AMR exome

AF:

0.139

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00668

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000324

Gnomad4 OTH exome

AF:

0.00500

GnomAD4 genome

AF:

0.0104

AC:

1576

AN:

152196

Hom.:

Cov.:

AF XY:

0.0116

AC XY:

866

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.00197

Gnomad4 AMR

AF:

0.0919

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00811

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.0189

Alfa

AF:

0.00422

Hom.:

Bravo

AF:

0.0189

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.0145

AC:

1764

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

ATG2B-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 26, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.84

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.090

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.091

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.62

LIST_S2

Uncertain

0.91

MetaRNN

Benign

0.0021

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.77

PROVEAN

Uncertain

-4.2

REVEL

Benign

0.26

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0030

Polyphen

0.30

Vest4

0.32

MutPred

0.45

Gain of disorder (P = 0.0996);

MPC

0.72

ClinPred

0.067

GERP RS

-2.7

Varity_R

0.57

gMVP

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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