rs1376326939

Variant names:

• chr11-72814467-G-A
• rs1376326939
• NM_033388.2:c.22G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-72814467-G-A
• chr11-72814467-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033388.2(ATG16L2):​c.22G>A​(p.Gly8Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000265 in 1,511,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: ATG16L2 NM_033388.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.239
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05736214).

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.22G>A	p.Gly8Ser	missense	Exon 1 of 18	NP_203746.1	Q8NAA4-1
	ATG16L2	NM_001318766.2		c.-417G>A		5_prime_UTR	Exon 1 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.22G>A	p.Gly8Ser	missense	Exon 1 of 18	ENSP00000326340.5	Q8NAA4-1
	ATG16L2	ENST00000534905.5	TSL:1	c.22G>A	p.Gly8Ser	missense	Exon 1 of 6	ENSP00000441189.1	F5GWZ9
	ATG16L2	ENST00000540567.1	TSL:1	c.34G>A	p.Gly12Ser	missense	Exon 1 of 3	ENSP00000443569.1	H0YGJ8

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152124 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: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000799 AC: 1 AN: 125188 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000147 AC: 2 AN: 1359666 Hom.: 0 Cov.: 30 AF XY: 0.00000299 AC XY: 2 AN XY: 668548

African (AFR) AF: 0.00 AC: 0 AN: 28786

American (AMR) AF: 0.00 AC: 0 AN: 33798

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24240

East Asian (EAS) AF: 0.00 AC: 0 AN: 32460

South Asian (SAS) AF: 0.0000131 AC: 1 AN: 76318

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46120

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4332

European-Non Finnish (NFE) AF: 9.45e-7 AC: 1 AN: 1057668

Other (OTH) AF: 0.00 AC: 0 AN: 55944

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152124 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74306

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.10
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	13
DANN	Benign	0.91
DEOGEN2	Benign	0.0083	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.064	D
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.24
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.087
Sift	Benign	0.18	T
Sift4G	Benign	0.094	T
Polyphen		0.0060	B
Vest4		0.093
MutPred		0.26		Gain of glycosylation at G8 (P = 0.0026)
MVP		0.11
MPC		0.28
ClinPred		0.069	T
GERP RS		0.26
PromoterAI		-0.010	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.056
gMVP		0.058
Mutation Taster		=99/1	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: rs1376326939; hg19: chr11-72525512;