Variant 11-64910626-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_015104.3(ATG2A):c.1697G>A(p.Arg566His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00439 in 1,601,918 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0063 ( 12 hom., cov: 33)

Exomes 𝑓: 0.0042 ( 94 hom. )

Consequence

ATG2A
NM_015104.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.605

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020740032).

BP6

Variant 11-64910626-C-T is Benign according to our data. Variant chr11-64910626-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00627 (955/152276) while in subpopulation EAS AF= 0.025 (129/5168). AF 95% confidence interval is 0.0215. There are 12 homozygotes in gnomad4. There are 592 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATG2A	NM_015104.3 linkuse as main transcript	c.1697G>A	p.Arg566His	missense_variant	12/41	ENST00000377264.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATG2A	ENST00000377264.8 linkuse as main transcript	c.1697G>A	p.Arg566His	missense_variant	12/41	1	NM_015104.3	P1	Q2TAZ0-1
ATG2A	ENST00000418259.5 linkuse as main transcript	c.1103G>A	p.Arg368His	missense_variant	8/37	5

Frequencies

GnomAD3 genomes

AF:

0.00628

AC:

955

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00281

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.0249

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.0427

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00423

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00709

AC:

1615

AN:

227782

Hom.:

AF XY:

0.00696

AC XY:

860

AN XY:

123598

show subpopulations

Gnomad AFR exome

AF:

0.000142

Gnomad AMR exome

AF:

0.000862

Gnomad ASJ exome

AF:

0.000209

Gnomad EAS exome

AF:

0.0239

Gnomad SAS exome

AF:

0.00120

Gnomad FIN exome

AF:

0.0386

Gnomad NFE exome

AF:

0.00374

Gnomad OTH exome

AF:

0.00638

GnomAD4 exome

AF:

0.00419

AC:

6079

AN:

1449642

Hom.:

Cov.:

AF XY:

0.00424

AC XY:

3053

AN XY:

720226

show subpopulations

Gnomad4 AFR exome

AF:

0.000271

Gnomad4 AMR exome

AF:

0.00137

Gnomad4 ASJ exome

AF:

0.000386

Gnomad4 EAS exome

AF:

0.0350

Gnomad4 SAS exome

AF:

0.00104

Gnomad4 FIN exome

AF:

0.0376

Gnomad4 NFE exome

AF:

0.00216

Gnomad4 OTH exome

AF:

0.00352

GnomAD4 genome

AF:

0.00627

AC:

955

AN:

152276

Hom.:

Cov.:

AF XY:

0.00795

AC XY:

592

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000553

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.0250

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.0427

Gnomad4 NFE

AF:

0.00423

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00463

Hom.:

Bravo

AF:

0.00324

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.00373

AC:

ExAC

AF:

0.00601

AC:

727

Asia WGS

AF:

0.00808

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.76

MetaRNN

Benign

0.0021

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.1

MutationTaster

Benign

0.95

N;N

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.7

REVEL

Benign

0.030

Sift

Benign

0.10

Sift4G

Benign

0.22

Polyphen

0.0040

Vest4

0.31

MVP

0.082

MPC

0.19

ClinPred

0.0088

GERP RS

3.1

Varity_R

0.028

gMVP

0.32

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over