Variant 14-96311131-G-C 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.4147C>G(p.Gln1383Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 1,610,334 control chromosomes in the GnomAD database, including 131,674 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.32 ( 9152 hom., cov: 32)

Exomes 𝑓: 0.40 ( 122522 hom. )

Consequence

ATG2B
NM_018036.7 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.13

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:

ATG2B (HGNC:):

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=0.0022884905).

BP6

Variant 14-96311131-G-C is Benign according to our data. Variant chr14-96311131-G-C is described in ClinVar as [Benign]. Clinvar id is 1269383.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATG2B	NM_018036.7 linkuse as main transcript	c.4147C>G	p.Gln1383Glu	missense_variant	28/42	ENST00000359933.6	NP_060506.6	Q96BY7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATG2B	ENST00000359933.6 linkuse as main transcript	c.4147C>G	p.Gln1383Glu	missense_variant	28/42	5	NM_018036.7	ENSP00000353010.4		Q96BY7
ATG2B	ENST00000261834.9 linkuse as main transcript	n.133C>G		non_coding_transcript_exon_variant	1/14	2

Frequencies

GnomAD3 genomes

AF:

0.325

AC:

49310

AN:

151870

Hom.:

9153

Cov.:

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.323

Gnomad AMR

AF:

0.395

Gnomad ASJ

AF:

0.321

Gnomad EAS

AF:

0.199

Gnomad SAS

AF:

0.232

Gnomad FIN

AF:

0.348

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.423

Gnomad OTH

AF:

0.314

GnomAD3 exomes

AF:

0.357

AC:

88892

AN:

248692

Hom.:

17285

AF XY:

0.355

AC XY:

47751

AN XY:

134474

show subpopulations

Gnomad AFR exome

AF:

0.153

Gnomad AMR exome

AF:

0.435

Gnomad ASJ exome

AF:

0.335

Gnomad EAS exome

AF:

0.201

Gnomad SAS exome

AF:

0.237

Gnomad FIN exome

AF:

0.354

Gnomad NFE exome

AF:

0.425

Gnomad OTH exome

AF:

0.346

GnomAD4 exome

AF:

0.402

AC:

586515

AN:

1458346

Hom.:

122522

Cov.:

AF XY:

0.398

AC XY:

288430

AN XY:

725468

show subpopulations

Gnomad4 AFR exome

AF:

0.145

Gnomad4 AMR exome

AF:

0.432

Gnomad4 ASJ exome

AF:

0.335

Gnomad4 EAS exome

AF:

0.198

Gnomad4 SAS exome

AF:

0.244

Gnomad4 FIN exome

AF:

0.361

Gnomad4 NFE exome

AF:

0.435

Gnomad4 OTH exome

AF:

0.359

GnomAD4 genome

AF:

0.324

AC:

49319

AN:

151988

Hom.:

9152

Cov.:

AF XY:

0.320

AC XY:

23766

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.159

Gnomad4 AMR

AF:

0.395

Gnomad4 ASJ

AF:

0.321

Gnomad4 EAS

AF:

0.199

Gnomad4 SAS

AF:

0.233

Gnomad4 FIN

AF:

0.348

Gnomad4 NFE

AF:

0.423

Gnomad4 OTH

AF:

0.310

Alfa

AF:

0.394

Hom.:

9221

Bravo

AF:

0.323

TwinsUK

AF:

0.460

AC:

1707

ALSPAC

AF:

0.442

AC:

1704

ESP6500AA

AF:

0.171

AC:

755

ESP6500EA

AF:

0.423

AC:

3634

ExAC

AF:

0.353

AC:

42859

Asia WGS

AF:

0.203

AC:

705

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.20

DEOGEN2

Benign

0.00039

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.59

MetaRNN

Benign

0.0023

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.69

PrimateAI

Benign

0.24

PROVEAN

Benign

0.25

REVEL

Benign

0.10

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.024

MPC

0.18

ClinPred

0.0042

GERP RS

2.5

Varity_R

0.038

gMVP

0.13

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