NM_018036.7:c.3370A>G

Variant names:

• chr14-96315575-T-C
• rs9323945
• NM_018036.7:c.3370A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018036.7(ATG2B):​c.3370A>G​(p.Asn1124Asp) variant causes a missense change. The variant allele was found at a frequency of 0.975 in 1,613,490 control chromosomes in the GnomAD database, including 769,107 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N1124Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.98 (72598 hom., cov: 31)
  • Exomes 𝑓: 0.98 (696509 hom.)
• Consequence: ATG2B NM_018036.7 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.90
• Publications: 31 publications found

Genes affected

ATG2B (HGNC:20187): (autophagy related 2B) This gene encodes a protein required for autophagy. The encoded protein is involved in autophagosome formation. A germline duplication of a region that includes this gene is associated with predisposition to myeloid malignancies. [provided by RefSeq, Jul 2016]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.7062505E-7).
• BP6: Variant 14-96315575-T-C is Benign according to our data. Variant chr14-96315575-T-C is described in ClinVar as Benign. ClinVar VariationId is 1238176.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.987 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018036.7. 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
	ATG2B	NM_018036.7	MANE Select	c.3370A>G	p.Asn1124Asp	missense	Exon 22 of 42	NP_060506.6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG2B	ENST00000359933.6	TSL:5 MANE Select	c.3370A>G	p.Asn1124Asp	missense	Exon 22 of 42	ENSP00000353010.4	Q96BY7
	ATG2B	ENST00000938845.1		c.3370A>G	p.Asn1124Asp	missense	Exon 22 of 42	ENSP00000608904.1

Frequencies

GnomAD3 genomes AF: 0.975 AC: 148374 AN: 152154 Hom.: 72540 Cov.: 31

Gnomad AFR AF: 0.995

Gnomad AMI AF: 0.981

Gnomad AMR AF: 0.949

Gnomad ASJ AF: 0.992

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.851

Gnomad FIN AF: 0.992

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.990

Gnomad OTH AF: 0.974

GnomAD2 exomes AF: 0.947 AC: 236322 AN: 249574 AF XY: 0.947

Gnomad AFR exome AF: 0.996

Gnomad AMR exome AF: 0.916

Gnomad ASJ exome AF: 0.995

Gnomad EAS exome AF: 0.757

Gnomad FIN exome AF: 0.992

Gnomad NFE exome AF: 0.990

Gnomad OTH exome AF: 0.963

GnomAD4 exome AF: 0.975 AC: 1424982 AN: 1461218 Hom.: 696509 Cov.: 39 AF XY: 0.972 AC XY: 706902 AN XY: 726960

African (AFR) AF: 0.996 AC: 33342 AN: 33474

American (AMR) AF: 0.920 AC: 41133 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.994 AC: 25986 AN: 26134

East Asian (EAS) AF: 0.796 AC: 31590 AN: 39672

South Asian (SAS) AF: 0.868 AC: 74835 AN: 86214

European-Finnish (FIN) AF: 0.992 AC: 52940 AN: 53386

Middle Eastern (MID) AF: 0.980 AC: 5649 AN: 5766

European-Non Finnish (NFE) AF: 0.991 AC: 1101267 AN: 1111504

Other (OTH) AF: 0.965 AC: 58240 AN: 60368

GnomAD4 genome AF: 0.975 AC: 148486 AN: 152272 Hom.: 72598 Cov.: 31 AF XY: 0.971 AC XY: 72312 AN XY: 74450

African (AFR) AF: 0.995 AC: 41363 AN: 41556

American (AMR) AF: 0.948 AC: 14504 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.992 AC: 3444 AN: 3472

East Asian (EAS) AF: 0.771 AC: 3979 AN: 5164

South Asian (SAS) AF: 0.851 AC: 4102 AN: 4820

European-Finnish (FIN) AF: 0.992 AC: 10531 AN: 10618

Middle Eastern (MID) AF: 0.983 AC: 289 AN: 294

European-Non Finnish (NFE) AF: 0.990 AC: 67333 AN: 68032

Other (OTH) AF: 0.970 AC: 2046 AN: 2110

Alfa AF: 0.981 Hom.: 214022

Bravo AF: 0.975

TwinsUK AF: 0.989 AC: 3669

ALSPAC AF: 0.993 AC: 3828

ESP6500AA AF: 0.995 AC: 4240

ESP6500EA AF: 0.992 AC: 8463

ExAC AF: 0.948 AC: 114787

Asia WGS AF: 0.811 AC: 2822 AN: 3478

EpiCase AF: 0.991

EpiControl AF: 0.989

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.045
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	19
DANN	Benign	0.46
DEOGEN2	Benign	0.00056	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.21	T
MetaRNN	Benign	5.7e-7	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.5	N
PhyloP100		3.9
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	1.6	N
REVEL	Benign	0.14
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.045
MPC		0.19
ClinPred		0.0058	T
GERP RS		5.2
Varity_R		0.098
gMVP		0.21
Mutation Taster		=99/1	polymorphism (auto)

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: rs9323945; hg19: chr14-96781912; COSMIC: COSV107241594; COSMIC: COSV107241594;