Variant 14-96289721-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_018036.7(ATG2B):c.5941C>G(p.Arg1981Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00239 in 1,614,172 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 11 hom. )

Consequence

ATG2B
NM_018036.7 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 5.56

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007583976).

BP6

Variant 14-96289721-G-C is Benign according to our data. Variant chr14-96289721-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3045990.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATG2B	NM_018036.7 linkuse as main transcript	c.5941C>G	p.Arg1981Gly	missense_variant	41/42	ENST00000359933.6	NP_060506.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATG2B	ENST00000359933.6 linkuse as main transcript	c.5941C>G	p.Arg1981Gly	missense_variant	41/42	5	NM_018036.7	ENSP00000353010	P1
ATG2B	ENST00000555263.1 linkuse as main transcript	n.227C>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.00208

AC:

316

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00353

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.0101

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00194

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00243

AC:

610

AN:

251470

Hom.:

AF XY:

0.00241

AC XY:

328

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.00188

Gnomad ASJ exome

AF:

0.000694

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00323

Gnomad FIN exome

AF:

0.00938

Gnomad NFE exome

AF:

0.00185

Gnomad OTH exome

AF:

0.00310

GnomAD4 exome

AF:

0.00243

AC:

3549

AN:

1461868

Hom.:

Cov.:

AF XY:

0.00242

AC XY:

1763

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.00181

Gnomad4 ASJ exome

AF:

0.000459

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00323

Gnomad4 FIN exome

AF:

0.00874

Gnomad4 NFE exome

AF:

0.00229

Gnomad4 OTH exome

AF:

0.00217

GnomAD4 genome

AF:

0.00207

AC:

316

AN:

152304

Hom.:

Cov.:

AF XY:

0.00248

AC XY:

185

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.00353

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.0101

Gnomad4 NFE

AF:

0.00194

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00180

Hom.:

Bravo

AF:

0.00153

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.00208

AC:

253

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00164

EpiControl

AF:

0.00261

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ATG2B-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 27, 2023

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.049

Eigen

Benign

0.12

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.89

MetaRNN

Benign

0.0076

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.11

Sift

Benign

0.080

Sift4G

Benign

0.12

Polyphen

0.0

Vest4

0.40

MVP

0.40

MPC

0.78

ClinPred

0.046

GERP RS

5.4

Varity_R

0.34

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.

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