chr2-233272973-G-T

Position:

• chr2-233272973-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_030803.7(ATG16L1):​c.715G>T​(p.Asp239Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATG16L1 NM_030803.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.26

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATG16L1	NM_030803.7	c.715G>T	p.Asp239Tyr	missense_variant	7/18	ENST00000392017.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATG16L1	ENST00000392017.9	c.715G>T	p.Asp239Tyr	missense_variant	7/18	1	NM_030803.7	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 30, 2024

The c.715G>T (p.D239Y) alteration is located in exon 7 (coding exon 7) of the ATG16L1 gene. This alteration results from a G to T substitution at nucleotide position 715, causing the aspartic acid (D) at amino acid position 239 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	.;T;T;.;T;.;.;.
Eigen	Pathogenic	0.90
Eigen_PC	Pathogenic	0.91
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.65	D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.31	T
MutationAssessor	Uncertain	2.0	.;M;.;.;.;.;M;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-2.6	D;D;D;N;D;D;D;N
REVEL	Uncertain	0.42
Sift	Uncertain	0.0060	D;D;D;D;.;D;D;D
Sift4G	Uncertain	0.015	D;D;D;D;D;D;D;D
Polyphen		1.0	.;D;.;D;.;.;D;.
Vest4		0.84
MutPred		0.47		.;Gain of phosphorylation at D239 (P = 0.0033);.;.;.;.;Gain of phosphorylation at D239 (P = 0.0033);Gain of phosphorylation at D239 (P = 0.0033);
MVP		0.64
MPC		1.7
ClinPred		0.94	D
GERP RS		6.1
Varity_R		0.26
gMVP		0.59

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-234181619;