rs77228473

Variant names:

• chr11-64898810-C-G
• rs77228473
• NM_015104.3:c.4497G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015104.3(ATG2A):​c.4497G>C​(p.Glu1499Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATG2A NM_015104.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900
• Publications: 1 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14385486).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG2A	NM_015104.3	MANE Select	c.4497G>C	p.Glu1499Asp	missense	Exon 32 of 41	NP_055919.2
	ATG2A	NM_001367972.1		c.4479G>C	p.Glu1493Asp	missense	Exon 32 of 41	NP_001354901.1
	ATG2A	NM_001367971.1		c.4473G>C	p.Glu1491Asp	missense	Exon 32 of 41	NP_001354900.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG2A	ENST00000377264.8	TSL:1 MANE Select	c.4497G>C	p.Glu1499Asp	missense	Exon 32 of 41	ENSP00000366475.3
	ATG2A	ENST00000418259.5	TSL:5	c.3906G>C	p.Glu1302Asp	missense	Exon 28 of 37	ENSP00000413716.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.7
DANN	Uncertain	0.98
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		-0.090
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.020	N
REVEL	Benign	0.065
Sift	Benign	0.43	T
Sift4G	Benign	0.60	T
Polyphen		0.90	P
Vest4		0.34
MutPred		0.17		Loss of phosphorylation at Y1496 (P = 0.0879)
MVP		0.17
MPC		0.48
ClinPred		0.39	T
GERP RS		2.4
Varity_R		0.036
gMVP		0.12
Mutation Taster		=95/5	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: rs77228473; hg19: chr11-64666282;