rs774060355

Variant names:

• chr11-72814482-C-G
• rs774060355
• NM_033388.2:c.37C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-72814482-C-G
• chr11-72814482-C-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.37C>G​(p.Arg13Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000728 in 1,373,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R13C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: ATG16L2 NM_033388.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600
• 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=0.13769081).

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.37C>G	p.Arg13Gly	missense	Exon 1 of 18	NP_203746.1	Q8NAA4-1
	ATG16L2	NM_001318766.2		c.-402C>G		5_prime_UTR	Exon 1 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.37C>G	p.Arg13Gly	missense	Exon 1 of 18	ENSP00000326340.5	Q8NAA4-1
	ATG16L2	ENST00000534905.5	TSL:1	c.37C>G	p.Arg13Gly	missense	Exon 1 of 6	ENSP00000441189.1	F5GWZ9
	ATG16L2	ENST00000540567.1	TSL:1	c.49C>G	p.Arg17Gly	missense	Exon 1 of 3	ENSP00000443569.1	H0YGJ8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.28e-7 AC: 1 AN: 1373066 Hom.: 0 Cov.: 30 AF XY: 0.00000148 AC XY: 1 AN XY: 675960

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 29440

American (AMR) AF: 0.00 AC: 0 AN: 34600

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24556

East Asian (EAS) AF: 0.00 AC: 0 AN: 33528

South Asian (SAS) AF: 0.00 AC: 0 AN: 77286

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47654

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4778

European-Non Finnish (NFE) AF: 9.39e-7 AC: 1 AN: 1064670

Other (OTH) AF: 0.00 AC: 0 AN: 56554

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	11
DANN	Benign	0.93
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.42	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.32	N
PhyloP100		0.0060
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.058
Sift	Benign	0.61	T
Sift4G	Benign	0.56	T
Polyphen		1.0	D
Vest4		0.11
MutPred		0.36		Gain of loop (P = 0.0079)
MVP		0.11
MPC		1.1
ClinPred		0.055	T
GERP RS		-2.4
PromoterAI		0.076	Neutral
Varity_R		0.057
gMVP		0.15
Mutation Taster		=98/2	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: rs774060355; hg19: chr11-72525527;