11-72822491-C-T

Position:

• chr11-72822491-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033388.2(ATG16L2):​c.658C>T​(p.Arg220Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00278 in 1,612,914 control chromosomes in the GnomAD database, including 216 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.0034 (32 hom., cov: 33)
  • Exomes 𝑓: 0.0027 (184 hom.)
• Consequence: ATG16L2 NM_033388.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.653

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014125407).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.091 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATG16L2	NM_033388.2	c.658C>T	p.Arg220Trp	missense_variant	6/18	ENST00000321297.10	NP_203746.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATG16L2	ENST00000321297.10	c.658C>T	p.Arg220Trp	missense_variant	6/18	1	NM_033388.2	ENSP00000326340.5

Frequencies

GnomAD3 genomes AF: 0.00339 AC: 516 AN: 152038 Hom.: 32 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0979

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00701 AC: 1743 AN: 248570 Hom.: 91 AF XY: 0.00614 AC XY: 828 AN XY: 134858

Gnomad AFR exome AF: 0.0000625

Gnomad AMR exome AF: 0.000176

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0934

Gnomad SAS exome AF: 0.000524

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000712

Gnomad OTH exome AF: 0.00165

GnomAD4 exome AF: 0.00272 AC: 3966 AN: 1460758 Hom.: 184 Cov.: 34 AF XY: 0.00264 AC XY: 1922 AN XY: 726698

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000180

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0940

Gnomad4 SAS exome AF: 0.000441

Gnomad4 FIN exome AF: 0.0000375

Gnomad4 NFE exome AF: 0.0000369

Gnomad4 OTH exome AF: 0.00244

GnomAD4 genome AF: 0.00339 AC: 516 AN: 152156 Hom.: 32 Cov.: 33 AF XY: 0.00371 AC XY: 276 AN XY: 74388

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.000261

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0981

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00322 Hom.: 25

Bravo AF: 0.00391

ExAC AF: 0.00672 AC: 815

Asia WGS AF: 0.0180 AC: 62 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000594

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T;T;.
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.087	N
LIST_S2	Benign	0.82	T;T;T
MetaRNN	Benign	0.0014	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L;.;.
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-4.3	D;D;D
REVEL	Benign	0.15
Sift	Uncertain	0.026	D;D;D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		0.078	B;.;.
Vest4		0.23
MVP		0.45
MPC		1.6
ClinPred		0.049	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.27
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs11235604; hg19: chr11-72533536; COSMIC: COSV58362408; COSMIC: COSV58362408;