11-72822106-A-G

Variant names:

• chr11-72822106-A-G
• rs1232435238
• NM_033388.2:c.455A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033388.2(ATG16L2):​c.455A>G​(p.Gln152Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000209 in 1,384,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 33)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: ATG16L2 NM_033388.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.327

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09056702).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG16L2	NM_033388.2	c.455A>G	p.Gln152Arg	missense_variant	Exon 5 of 18	ENST00000321297.10	NP_203746.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG16L2	ENST00000321297.10	c.455A>G	p.Gln152Arg	missense_variant	Exon 5 of 18	1	NM_033388.2	ENSP00000326340.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000209 AC: 29 AN: 1384614 Hom.: 0 Cov.: 33 AF XY: 0.0000277 AC XY: 19 AN XY: 685650

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000249

Gnomad4 OTH exome AF: 0.0000347

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 28, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.455A>G (p.Q152R) alteration is located in exon 5 (coding exon 5) of the ATG16L2 gene. This alteration results from a A to G substitution at nucleotide position 455, causing the glutamine (Q) at amino acid position 152 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	8.0
DANN	Benign	0.28
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.43	T
M_CAP	Uncertain	0.088	D
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.6	L
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.14
Sift	Benign	0.30	T
Sift4G	Benign	0.75	T
Polyphen		0.0	B
Vest4		0.18
MutPred		0.47		Gain of MoRF binding (P = 0.0257);
MVP		0.55
MPC		1.7
ClinPred		0.092	T
GERP RS		0.87
Varity_R		0.10
gMVP		0.17

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

Publications

LitVar

Other links and lift over

dbSNP: rs1232435238; hg19: chr11-72533151;