11-64895176-C-T

Variant names:

• chr11-64895176-C-T
• rs773533718
• NM_015104.3:c.5614G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015104.3(ATG2A):​c.5614G>A​(p.Val1872Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,612,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1872L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: ATG2A NM_015104.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.53
• Publications: 0 publications found

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]

ENSG00000308350 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35305032).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015104.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG2A	NM_015104.3	MANE Select	c.5614G>A	p.Val1872Met	missense	Exon 41 of 41	NP_055919.2	Q2TAZ0-1
	ATG2A	NM_001367972.1		c.5596G>A	p.Val1866Met	missense	Exon 41 of 41	NP_001354901.1
	ATG2A	NM_001367971.1		c.5590G>A	p.Val1864Met	missense	Exon 41 of 41	NP_001354900.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG2A	ENST00000377264.8	TSL:1 MANE Select	c.5614G>A	p.Val1872Met	missense	Exon 41 of 41	ENSP00000366475.3	Q2TAZ0-1
	ATG2A	ENST00000879824.1		c.5596G>A	p.Val1866Met	missense	Exon 41 of 41	ENSP00000549883.1
	ATG2A	ENST00000879823.1		c.5590G>A	p.Val1864Met	missense	Exon 41 of 41	ENSP00000549882.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152212 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000123 AC: 18 AN: 1460730 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10 AN XY: 726642

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52872

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000153 AC: 17 AN: 1111580

Other (OTH) AF: 0.0000166 AC: 1 AN: 60362

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152212 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74356

African (AFR) AF: 0.00 AC: 0 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		1.5
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.25
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.015	D
Polyphen		1.0	D
Vest4		0.37
MutPred		0.56		Gain of disorder (P = 0.1017)
MVP		0.40
MPC		1.4
ClinPred		0.99	D
GERP RS		3.8
Varity_R		0.31
gMVP		0.89
Mutation Taster		=69/31	polymorphism

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

Other links and lift over

dbSNP: rs773533718; hg19: chr11-64662648; COSMIC: COSV63475526; COSMIC: COSV63475526;