11-72822214-C-A

Variant names:

• chr11-72822214-C-A
• rs771836595
• NM_033388.2:c.563C>A

Variant summary

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

The NM_033388.2(ATG16L2):​c.563C>A​(p.Ala188Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000148 in 1,352,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. A188G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: ATG16L2 NM_033388.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.245
• Publications: 0 publications found

Genes affected

ATG16L2 (HGNC:25464): (autophagy related 16 like 2) Predicted to be involved in autophagosome assembly and negative stranded viral RNA replication. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.30001548).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033388.2. 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
	ATG16L2	NM_033388.2	MANE Select	c.563C>A	p.Ala188Glu	missense	Exon 5 of 18	NP_203746.1	Q8NAA4-1
	ATG16L2	NM_001318766.2		c.245C>A	p.Ala82Glu	missense	Exon 5 of 18	NP_001305695.1	Q8NAA4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG16L2	ENST00000321297.10	TSL:1 MANE Select	c.563C>A	p.Ala188Glu	missense	Exon 5 of 18	ENSP00000326340.5	Q8NAA4-1
	ATG16L2	ENST00000534905.5	TSL:1	c.318+4359C>A		intron	N/A	ENSP00000441189.1	F5GWZ9
	ATG16L2	ENST00000439504.6	TSL:1	n.590C>A		non_coding_transcript_exon	Exon 5 of 16

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000148 AC: 2 AN: 1352798 Hom.: 0 Cov.: 33 AF XY: 0.00000300 AC XY: 2 AN XY: 667442

African (AFR) AF: 0.00 AC: 0 AN: 27784

American (AMR) AF: 0.00 AC: 0 AN: 29474

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23626

East Asian (EAS) AF: 0.00 AC: 0 AN: 33556

South Asian (SAS) AF: 0.00 AC: 0 AN: 76278

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33116

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4088

European-Non Finnish (NFE) AF: 0.00000187 AC: 2 AN: 1068558

Other (OTH) AF: 0.00 AC: 0 AN: 56318

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.042	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.66	T
M_CAP	Pathogenic	0.86	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.52	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-0.24
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.63	N
REVEL	Uncertain	0.30
Sift	Benign	0.097	T
Sift4G	Benign	0.15	T
Polyphen		0.60	P
Vest4		0.29
MutPred		0.48		Loss of helix (P = 0.028)
MVP		0.66
MPC		1.8
ClinPred		0.66	D
GERP RS		1.3
PromoterAI		-0.052	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.092
gMVP		0.19
Mutation Taster		=93/7	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: rs771836595; hg19: chr11-72533259;