NM_033388.2:c.415G>C

Variant names:

• chr11-72822066-G-C
• rs752286622
• NM_033388.2:c.415G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000086 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: ATG16L2 NM_033388.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.12
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09614375).

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.415G>C	p.Val139Leu	missense	Exon 5 of 18	NP_203746.1	Q8NAA4-1
	ATG16L2	NM_001318766.2		c.97G>C	p.Val33Leu	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.415G>C	p.Val139Leu	missense	Exon 5 of 18	ENSP00000326340.5	Q8NAA4-1
	ATG16L2	ENST00000534905.5	TSL:1	c.318+4211G>C		intron	N/A	ENSP00000441189.1	F5GWZ9
	ATG16L2	ENST00000439504.6	TSL:1	n.442G>C		non_coding_transcript_exon	Exon 5 of 16

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

GnomAD2 exomes AF: 0.0000663 AC: 9 AN: 135686 AF XY: 0.0000648

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 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

African (AFR) AF: 0.000103 AC: 3 AN: 28998

American (AMR) AF: 0.00 AC: 0 AN: 29414

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22588

East Asian (EAS) AF: 0.00 AC: 0 AN: 35664

South Asian (SAS) AF: 0.00 AC: 0 AN: 75518

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34728

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4004

European-Non Finnish (NFE) AF: 0.000149 AC: 161 AN: 1082358

Other (OTH) AF: 0.000421 AC: 24 AN: 56940

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

African (AFR) AF: 0.00 AC: 0 AN: 41068

American (AMR) AF: 0.00 AC: 0 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5098

South Asian (SAS) AF: 0.00 AC: 0 AN: 4766

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 296

European-Non Finnish (NFE) AF: 0.000192 AC: 13 AN: 67592

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.0000435 Hom.: 0

Bravo AF: 0.0000945

ExAC AF: 0.0000346 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		2.1
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
PromoterAI		0.083	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.047
Mutation Taster		=95/5	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: rs752286622; hg19: chr11-72533111;