chr11-64895397-C-T

Variant names:

• chr11-64895397-C-T
• rs148192310
• NM_015104.3:c.5473G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_015104.3(ATG2A):​c.5473G>A​(p.Val1825Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00148 in 1,607,706 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0081 (17 hom., cov: 33)
  • Exomes 𝑓: 0.00079 (17 hom.)
• Consequence: ATG2A NM_015104.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.62
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0030631423).
• BP6: Variant 11-64895397-C-T is Benign according to our data. Variant chr11-64895397-C-T is described in ClinVar as Benign. ClinVar VariationId is 716422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0081 (1234/152260) while in subpopulation AFR AF = 0.0278 (1153/41544). AF 95% confidence interval is 0.0264. There are 17 homozygotes in GnomAd4. There are 610 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 17 gene

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.5473G>A	p.Val1825Ile	missense	Exon 40 of 41	NP_055919.2	Q2TAZ0-1
	ATG2A	NM_001367972.1		c.5455G>A	p.Val1819Ile	missense	Exon 40 of 41	NP_001354901.1
	ATG2A	NM_001367971.1		c.5449G>A	p.Val1817Ile	missense	Exon 40 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.5473G>A	p.Val1825Ile	missense	Exon 40 of 41	ENSP00000366475.3	Q2TAZ0-1
	ATG2A	ENST00000879824.1		c.5455G>A	p.Val1819Ile	missense	Exon 40 of 41	ENSP00000549883.1
	ATG2A	ENST00000879823.1		c.5449G>A	p.Val1817Ile	missense	Exon 40 of 41	ENSP00000549882.1

Frequencies

GnomAD3 genomes AF: 0.00810 AC: 1232 AN: 152142 Hom.: 17 Cov.: 33

Gnomad AFR AF: 0.0278

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00347

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00909

GnomAD2 exomes AF: 0.00204 AC: 480 AN: 235742 AF XY: 0.00163

Gnomad AFR exome AF: 0.0278

Gnomad AMR exome AF: 0.00127

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000289

Gnomad OTH exome AF: 0.00157

GnomAD4 exome AF: 0.000786 AC: 1144 AN: 1455446 Hom.: 17 Cov.: 32 AF XY: 0.000698 AC XY: 505 AN XY: 723422

African (AFR) AF: 0.0289 AC: 964 AN: 33378

American (AMR) AF: 0.00142 AC: 63 AN: 44226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25828

East Asian (EAS) AF: 0.00 AC: 0 AN: 39544

South Asian (SAS) AF: 0.0000700 AC: 6 AN: 85770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52526

Middle Eastern (MID) AF: 0.000728 AC: 4 AN: 5494

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1108714

Other (OTH) AF: 0.00153 AC: 92 AN: 59966

GnomAD4 genome AF: 0.00810 AC: 1234 AN: 152260 Hom.: 17 Cov.: 33 AF XY: 0.00819 AC XY: 610 AN XY: 74448

African (AFR) AF: 0.0278 AC: 1153 AN: 41544

American (AMR) AF: 0.00346 AC: 53 AN: 15308

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 67996

Other (OTH) AF: 0.00900 AC: 19 AN: 2112

Alfa AF: 0.00235 Hom.: 4

Bravo AF: 0.00897

ESP6500AA AF: 0.0234 AC: 103

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00241 AC: 292

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.2
DANN	Benign	0.79
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.0031	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.14	N
PhyloP100		-1.6
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.014
Sift	Benign	0.45	T
Sift4G	Benign	0.46	T
Polyphen		0.0030	B
Vest4		0.13
MVP		0.19
MPC		0.40
ClinPred		0.0010	T
GERP RS		-5.6
Varity_R		0.028
gMVP		0.23
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs148192310; hg19: chr11-64662869;