chr2-233251887-A-C

Variant names:

• chr2-233251887-A-C
• rs113377061
• NM_030803.7:c.60A>C

Variant summary

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

The NM_030803.7(ATG16L1):​c.60A>C​(p.Gln20His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q20Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ATG16L1 NM_030803.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25684008).

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.60A>C	p.Gln20His	missense	Exon 1 of 18	NP_110430.5
	ATG16L1	NM_001363742.2		c.60A>C	p.Gln20His	missense	Exon 1 of 19	NP_001350671.1	E7EVC7
	ATG16L1	NM_017974.4		c.60A>C	p.Gln20His	missense	Exon 1 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.60A>C	p.Gln20His	missense	Exon 1 of 18	ENSP00000375872.4	Q676U5-1
	ATG16L1	ENST00000392020.8	TSL:1	c.60A>C	p.Gln20His	missense	Exon 1 of 17	ENSP00000375875.4	Q676U5-2
	ATG16L1	ENST00000347464.9	TSL:1	c.60A>C	p.Gln20His	missense	Exon 1 of 14	ENSP00000318259.6	Q676U5-5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.038
FATHMM_MKL	Benign	0.56	D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.0
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.078
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.011	D
Polyphen		0.54	P
Vest4		0.15
MutPred		0.52		Gain of catalytic residue at Q20 (P = 0.2518)
MVP		0.56
MPC		0.75
ClinPred		0.96	D
GERP RS		3.6
PromoterAI		-0.030	Neutral
Varity_R		0.34
gMVP		0.21
Mutation Taster		=67/33	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: rs113377061; hg19: chr2-234160533;