rs200456427

Variant names:

• chr11-72822489-C-T
• rs200456427
• NM_033388.2:c.656C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033388.2(ATG16L2):​c.656C>T​(p.Ala219Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000502 in 1,612,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000053 (0 hom.)
• Consequence: ATG16L2 NM_033388.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0440
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2494998).

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.656C>T	p.Ala219Val	missense	Exon 6 of 18	NP_203746.1	Q8NAA4-1
	ATG16L2	NM_001318766.2		c.338C>T	p.Ala113Val	missense	Exon 6 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.656C>T	p.Ala219Val	missense	Exon 6 of 18	ENSP00000326340.5	Q8NAA4-1
	ATG16L2	ENST00000534905.5	TSL:1	c.318+4634C>T		intron	N/A	ENSP00000441189.1	F5GWZ9
	ATG16L2	ENST00000439504.6	TSL:1	n.683C>T		non_coding_transcript_exon	Exon 6 of 16

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152086 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000804 AC: 2 AN: 248622 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: 0.0000178

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000534 AC: 78 AN: 1460764 Hom.: 0 Cov.: 34 AF XY: 0.0000358 AC XY: 26 AN XY: 726702

African (AFR) AF: 0.00 AC: 0 AN: 33410

American (AMR) AF: 0.0000225 AC: 1 AN: 44504

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26070

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.00 AC: 0 AN: 86204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000675 AC: 75 AN: 1111524

Other (OTH) AF: 0.0000331 AC: 2 AN: 60334

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152204 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74428

African (AFR) AF: 0.00 AC: 0 AN: 41528

American (AMR) AF: 0.000131 AC: 2 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

EpiCase AF: 0.0000545

EpiControl AF: 0.0000594

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	0.12
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		-0.044
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.21
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.21
MVP		0.82
MPC		1.6
ClinPred		0.94	D
GERP RS		4.7
PromoterAI		-0.29	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.41
gMVP		0.43
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs200456427; hg19: chr11-72533534;