chr11-64895118-C-T

Variant names:

• chr11-64895118-C-T
• rs1477315197
• NM_015104.3:c.5672G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_015104.3(ATG2A):​c.5672G>A​(p.Arg1891His) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,612,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: ATG2A NM_015104.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.78
• 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]

ENSG00000308350 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.773

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.5672G>A	p.Arg1891His	missense	Exon 41 of 41	NP_055919.2	Q2TAZ0-1
	ATG2A	NM_001367972.1		c.5654G>A	p.Arg1885His	missense	Exon 41 of 41	NP_001354901.1
	ATG2A	NM_001367971.1		c.5648G>A	p.Arg1883His	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.5672G>A	p.Arg1891His	missense	Exon 41 of 41	ENSP00000366475.3	Q2TAZ0-1
	ATG2A	ENST00000879824.1		c.5654G>A	p.Arg1885His	missense	Exon 41 of 41	ENSP00000549883.1
	ATG2A	ENST00000879823.1		c.5648G>A	p.Arg1883His	missense	Exon 41 of 41	ENSP00000549882.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152214 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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000548 AC: 8 AN: 1460630 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 726636

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00000720 AC: 8 AN: 1111774

Other (OTH) AF: 0.00 AC: 0 AN: 60362

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152214 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74354

African (AFR) AF: 0.00 AC: 0 AN: 41452

American (AMR) AF: 0.00 AC: 0 AN: 15280

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68028

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Pathogenic	0.69
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.49	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.099	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.91	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		5.8
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Uncertain	0.44
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.84
MVP		0.35
MPC		1.6
ClinPred		1.0	D
GERP RS		4.0
Varity_R		0.82
gMVP		0.91
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs1477315197; hg19: chr11-64662590;