Variant 11-64895397-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_015104.3(ATG2A):c.5473G>A(p.Val1825Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00148 in 1,607,706 control chromosomes in the GnomAD database, including 34 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 (★★).

Frequency

Genomes: 𝑓 0.0081 ( 17 hom., cov: 33)

Exomes 𝑓: 0.00079 ( 17 hom. )

Consequence

ATG2A
NM_015104.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.62

Variant links:

Genes affected

ATG2A (HGNC:29028): (autophagy related 2A) Predicted to enable phosphatidylinositol-3-phosphate binding activity. Involved in autophagosome assembly. Predicted to be located in endoplasmic reticulum membrane; lipid droplet; and phagophore assembly site membrane. Predicted to be active in phagophore assembly site. Predicted to be extrinsic component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ATG2A 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=0.0030631423).

BP6

Variant 11-64895397-C-T is Benign according to our data. Variant chr11-64895397-C-T is described in ClinVar as [Benign]. Clinvar id is 716422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0081 (1234/152260) while in subpopulation AFR AF= 0.0278 (1153/41544). AF 95% confidence interval is 0.0264. There are 17 homozygotes in gnomad4. There are 610 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 17 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATG2A	NM_015104.3 linkuse as main transcript	c.5473G>A	p.Val1825Ile	missense_variant	40/41	ENST00000377264.8	NP_055919.2	Q2TAZ0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATG2A	ENST00000377264.8 linkuse as main transcript	c.5473G>A	p.Val1825Ile	missense_variant	40/41	1	NM_015104.3	ENSP00000366475.3		Q2TAZ0-1
ATG2A	ENST00000418259.5 linkuse as main transcript	c.4882G>A	p.Val1628Ile	missense_variant	36/37	5		ENSP00000413716.1		H7C3T2

Frequencies

GnomAD3 genomes

AF:

0.00810

AC:

1232

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0278

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00347

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00909

GnomAD3 exomes

AF:

0.00204

AC:

480

AN:

235742

Hom.:

AF XY:

0.00163

AC XY:

210

AN XY:

128748

show subpopulations

Gnomad AFR exome

AF:

0.0278

Gnomad AMR exome

AF:

0.00127

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000167

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000289

Gnomad OTH exome

AF:

0.00157

GnomAD4 exome

AF:

0.000786

AC:

1144

AN:

1455446

Hom.:

Cov.:

AF XY:

0.000698

AC XY:

505

AN XY:

723422

show subpopulations

Gnomad4 AFR exome

AF:

0.0289

Gnomad4 AMR exome

AF:

0.00142

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000700

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.00153

GnomAD4 genome

AF:

0.00810

AC:

1234

AN:

152260

Hom.:

Cov.:

AF XY:

0.00819

AC XY:

610

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0278

Gnomad4 AMR

AF:

0.00346

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00900

Alfa

AF:

0.00197

Hom.:

Bravo

AF:

0.00897

ESP6500AA

AF:

0.0234

AC:

103

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00241

AC:

292

Asia WGS

AF:

0.000866

AC:

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 18, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.2

DANN

Benign

0.79

DEOGEN2

Benign

0.012

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.57

T;T

MetaRNN

Benign

0.0031

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.14

N;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.39

N;.

REVEL

Benign

0.014

Sift

Benign

0.45

T;.

Sift4G

Benign

0.46

T;T

Polyphen

0.0030

B;.

Vest4

0.13

MVP

0.19

MPC

0.40

ClinPred

0.0010

GERP RS

-5.6

Varity_R

0.028

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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