NM_033388.2:c.597G>T

Variant names:

• chr11-72822248-G-T
• rs944873805
• NM_033388.2:c.597G>T

Variant summary

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

The NM_033388.2(ATG16L2):​c.597G>T​(p.Lys199Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ATG16L2 NM_033388.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194
• 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 2 ACMG points.

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

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.597G>T	p.Lys199Asn	missense	Exon 5 of 18	NP_203746.1	Q8NAA4-1
	ATG16L2	NM_001318766.2		c.279G>T	p.Lys93Asn	missense	Exon 5 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.597G>T	p.Lys199Asn	missense	Exon 5 of 18	ENSP00000326340.5	Q8NAA4-1
	ATG16L2	ENST00000534905.5	TSL:1	c.318+4393G>T		intron	N/A	ENSP00000441189.1	F5GWZ9
	ATG16L2	ENST00000439504.6	TSL:1	n.624G>T		non_coding_transcript_exon	Exon 5 of 16

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1346354 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 663638

African (AFR) AF: 0.00 AC: 0 AN: 27986

American (AMR) AF: 0.00 AC: 0 AN: 27670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23076

East Asian (EAS) AF: 0.00 AC: 0 AN: 34002

South Asian (SAS) AF: 0.00 AC: 0 AN: 74508

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32934

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3998

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1066042

Other (OTH) AF: 0.00 AC: 0 AN: 56138

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.80	T
M_CAP	Pathogenic	0.50	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		0.19
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.40
MutPred		0.50		Gain of methylation at R201 (P = 0.0866)
MVP		0.79
MPC		3.1
ClinPred		0.99	D
GERP RS		1.9
PromoterAI		0.16	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.59
gMVP		0.50
Mutation Taster		=87/13	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: rs944873805; hg19: chr11-72533293;