11-72822066-G-C

Position:

• chr11-72822066-G-C

Variant summary

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

The NM_033388.2(ATG16L2):​c.415G>C​(p.Val139Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000132 in 1,521,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000086 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: ATG16L2 NM_033388.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.12

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=0.09614375).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATG16L2	NM_033388.2	c.415G>C	p.Val139Leu	missense_variant	5/18	ENST00000321297.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATG16L2	ENST00000321297.10	c.415G>C	p.Val139Leu	missense_variant	5/18	1	NM_033388.2	P1

Frequencies

GnomAD3 genomes AF: 0.0000861 AC: 13 AN: 151012 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: 0.000192

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000663 AC: 9 AN: 135686 Hom.: 0 AF XY: 0.0000648 AC XY: 5 AN XY: 77120

Gnomad AFR exome AF: 0.000141

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000125

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000137 AC: 188 AN: 1370212 Hom.: 0 Cov.: 33 AF XY: 0.000138 AC XY: 94 AN XY: 679148

Gnomad4 AFR exome AF: 0.000103

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: 0.000149

Gnomad4 OTH exome AF: 0.000421

GnomAD4 genome AF: 0.0000861 AC: 13 AN: 151012 Hom.: 0 Cov.: 33 AF XY: 0.0000407 AC XY: 3 AN XY: 73764

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000192

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000435 Hom.: 0

Bravo AF: 0.0000945

ExAC AF: 0.0000346 AC: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	0.96	D;N
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.13
Sift	Benign	0.39	T
Sift4G	Benign	0.50	T
Polyphen		0.12	B
Vest4		0.15
MutPred		0.52		Loss of MoRF binding (P = 0.1514);
MVP		0.52
MPC		0.30
ClinPred		0.070	T
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.047

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: rs752286622; hg19: chr11-72533111;