2-233282700-G-A

Variant names:

• chr2-233282700-G-A
• NM_030803.7:c.1150G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_030803.7(ATG16L1):​c.1150G>A​(p.Ala384Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ATG16L1 NM_030803.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.77
• Publications: 0 publications found

Genes affected

ATG16L1 (HGNC:21498): (autophagy related 16 like 1) The protein encoded by this gene is part of a large protein complex that is necessary for autophagy, the major process by which intracellular components are targeted to lysosomes for degradation. Defects in this gene are a cause of susceptibility to inflammatory bowel disease type 10 (IBD10). Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jun 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.858

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030803.7. 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
	ATG16L1	NM_030803.7	MANE Select	c.1150G>A	p.Ala384Thr	missense	Exon 12 of 18	NP_110430.5
	ATG16L1	NM_001363742.2		c.1201G>A	p.Ala401Thr	missense	Exon 13 of 19	NP_001350671.1	E7EVC7
	ATG16L1	NM_017974.4		c.1093G>A	p.Ala365Thr	missense	Exon 11 of 17	NP_060444.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG16L1	ENST00000392017.9	TSL:1 MANE Select	c.1150G>A	p.Ala384Thr	missense	Exon 12 of 18	ENSP00000375872.4	Q676U5-1
	ATG16L1	ENST00000392020.8	TSL:1	c.1093G>A	p.Ala365Thr	missense	Exon 11 of 17	ENSP00000375875.4	Q676U5-2
	ATG16L1	ENST00000347464.9	TSL:1	c.661G>A	p.Ala221Thr	missense	Exon 8 of 14	ENSP00000318259.6	Q676U5-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461802 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727186

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111958

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

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	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.034	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Benign	-0.30	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		6.8
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.49
Sift	Benign	0.16	T
Sift4G	Benign	0.27	T
Polyphen		0.67	P
Vest4		0.79
MutPred		0.81		Loss of stability (P = 0.06)
MVP		0.82
MPC		1.2
ClinPred		0.97	D
GERP RS		5.8
Varity_R		0.51
gMVP		0.72
Mutation Taster		=45/55	disease causing

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

hg19: chr2-234191346;