Variant 14-96315575-T-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.3370A>G(p.Asn1124Asp) variant causes a missense change. The variant allele was found at a frequency of 0.975 in 1,613,490 control chromosomes in the GnomAD database, including 769,107 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 0.98 ( 72598 hom., cov: 31)

Exomes 𝑓: 0.98 ( 696509 hom. )

Consequence

ATG2B
NM_018036.7 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.90

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=5.7062505E-7).

BP6

Variant 14-96315575-T-C is Benign according to our data. Variant chr14-96315575-T-C is described in ClinVar as [Benign]. Clinvar id is 1238176.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.987 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.3370A>G	p.Asn1124Asp	missense_variant	22/42	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.3370A>G	p.Asn1124Asp	missense_variant	22/42	5	NM_018036.7	ENSP00000353010.4		Q96BY7

Frequencies

GnomAD3 genomes

AF:

0.975

AC:

148374

AN:

152154

Hom.:

72540

Cov.:

show subpopulations

Gnomad AFR

AF:

0.995

Gnomad AMI

AF:

0.981

Gnomad AMR

AF:

0.949

Gnomad ASJ

AF:

0.992

Gnomad EAS

AF:

0.770

Gnomad SAS

AF:

0.851

Gnomad FIN

AF:

0.992

Gnomad MID

AF:

0.978

Gnomad NFE

AF:

0.990

Gnomad OTH

AF:

0.974

GnomAD3 exomes

AF:

0.947

AC:

236322

AN:

249574

Hom.:

112584

AF XY:

0.947

AC XY:

128155

AN XY:

135382

show subpopulations

Gnomad AFR exome

AF:

0.996

Gnomad AMR exome

AF:

0.916

Gnomad ASJ exome

AF:

0.995

Gnomad EAS exome

AF:

0.757

Gnomad SAS exome

AF:

0.862

Gnomad FIN exome

AF:

0.992

Gnomad NFE exome

AF:

0.990

Gnomad OTH exome

AF:

0.963

GnomAD4 exome

AF:

0.975

AC:

1424982

AN:

1461218

Hom.:

696509

Cov.:

AF XY:

0.972

AC XY:

706902

AN XY:

726960

show subpopulations

Gnomad4 AFR exome

AF:

0.996

Gnomad4 AMR exome

AF:

0.920

Gnomad4 ASJ exome

AF:

0.994

Gnomad4 EAS exome

AF:

0.796

Gnomad4 SAS exome

AF:

0.868

Gnomad4 FIN exome

AF:

0.992

Gnomad4 NFE exome

AF:

0.991

Gnomad4 OTH exome

AF:

0.965

GnomAD4 genome

AF:

0.975

AC:

148486

AN:

152272

Hom.:

72598

Cov.:

AF XY:

0.971

AC XY:

72312

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.995

Gnomad4 AMR

AF:

0.948

Gnomad4 ASJ

AF:

0.992

Gnomad4 EAS

AF:

0.771

Gnomad4 SAS

AF:

0.851

Gnomad4 FIN

AF:

0.992

Gnomad4 NFE

AF:

0.990

Gnomad4 OTH

AF:

0.970

Alfa

AF:

0.982

Hom.:

143323

Bravo

AF:

0.975

TwinsUK

AF:

0.989

AC:

3669

ALSPAC

AF:

0.993

AC:

3828

ESP6500AA

AF:

0.995

AC:

4240

ESP6500EA

AF:

0.992

AC:

8463

ExAC

AF:

0.948

AC:

114787

Asia WGS

AF:

0.811

AC:

2822

AN:

3478

EpiCase

AF:

0.991

EpiControl

AF:

0.989

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

0.045

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Benign

0.46

DEOGEN2

Benign

0.00056

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.21

MetaRNN

Benign

5.7e-7

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.5

PrimateAI

Uncertain

0.55

PROVEAN

Benign

1.6

REVEL

Benign

0.14

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.045

MPC

0.19

ClinPred

0.0058

GERP RS

5.2

Varity_R

0.098

gMVP

0.21

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