dbSNP rs773533718: ATG2A:p.Val1872Leu (chr11-64895176-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015104.3(ATG2A):c.5614G>T(p.Val1872Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1872M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

ATG2A
NM_015104.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.53

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG2A	NM_015104.3 link	c.5614G>T	p.Val1872Leu	missense_variant	Exon 41 of 41	ENST00000377264.8	NP_055919.2	Q2TAZ0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG2A	ENST00000377264.8 link	c.5614G>T	p.Val1872Leu	missense_variant	Exon 41 of 41	1	NM_015104.3	ENSP00000366475.3		Q2TAZ0-1
ATG2A	ENST00000418259.5 link	c.5023G>T	p.Val1675Leu	missense_variant	Exon 37 of 37	5		ENSP00000413716.1		H7C3T2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000404

AC:

AN:

247556

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134204

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000903

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.050

T;.

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.97

D;D

M_CAP

Benign

0.032

MetaRNN

Uncertain

0.44

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

M;.

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-2.2

N;.

REVEL

Benign

0.19

Sift

Uncertain

0.022

D;.

Sift4G

Benign

0.11

T;D

Polyphen

1.0

D;.

Vest4

0.51

MutPred

0.56

Loss of catalytic residue at V1872 (P = 0.1104);.;

MVP

0.33

MPC

1.2

ClinPred

0.92

GERP RS

3.8

Varity_R

0.37

gMVP

0.92

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over