chr14-96302043-T-G

Variant names:

• chr14-96302043-T-G
• rs74719094
• NM_018036.7:c.5103A>C

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.5103A>C​(p.Arg1701Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00521 in 1,613,936 control chromosomes in the GnomAD database, including 582 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (85 hom., cov: 32)
  • Exomes 𝑓: 0.0047 (497 hom.)
• Consequence: ATG2B NM_018036.7 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.541
• Publications: 5 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=0.002118796).
• BP6: Variant 14-96302043-T-G is Benign according to our data. Variant chr14-96302043-T-G is described in ClinVar as Benign. ClinVar VariationId is 1281030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG2B	NM_018036.7	c.5103A>C	p.Arg1701Ser	missense_variant	Exon 34 of 42	ENST00000359933.6	NP_060506.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG2B	ENST00000359933.6	c.5103A>C	p.Arg1701Ser	missense_variant	Exon 34 of 42	5	NM_018036.7	ENSP00000353010.4
ATG2B	ENST00000261834.9	n.1089A>C		non_coding_transcript_exon_variant	Exon 7 of 14	2

Frequencies

GnomAD3 genomes AF: 0.0104 AC: 1575 AN: 152078 Hom.: 85 Cov.: 32

Gnomad AFR AF: 0.00198

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0919

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00809

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.0191

GnomAD2 exomes AF: 0.0201 AC: 5050 AN: 251356 AF XY: 0.0151

Gnomad AFR exome AF: 0.00148

Gnomad AMR exome AF: 0.139

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00729

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.0155

GnomAD4 exome AF: 0.00467 AC: 6828 AN: 1461740 Hom.: 497 Cov.: 30 AF XY: 0.00391 AC XY: 2842 AN XY: 727176

African (AFR) AF: 0.000986 AC: 33 AN: 33478

American (AMR) AF: 0.139 AC: 6190 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00668 AC: 265 AN: 39696

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000324 AC: 36 AN: 1111924

Other (OTH) AF: 0.00500 AC: 302 AN: 60386

GnomAD4 genome AF: 0.0104 AC: 1576 AN: 152196 Hom.: 85 Cov.: 32 AF XY: 0.0116 AC XY: 866 AN XY: 74404

African (AFR) AF: 0.00197 AC: 82 AN: 41538

American (AMR) AF: 0.0919 AC: 1404 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00811 AC: 42 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68004

Other (OTH) AF: 0.0189 AC: 40 AN: 2112

Alfa AF: 0.00540 Hom.: 93

Bravo AF: 0.0189

ESP6500AA AF: 0.00159 AC: 7

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.0145 AC: 1764

Asia WGS AF: 0.00491 AC: 17 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

ATG2B-related disorder Benign:1

Sep 26, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.090
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.091	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.62	D
LIST_S2	Uncertain	0.91	D
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		-0.54
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.26
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.30	B
Vest4		0.32
MutPred		0.45		Gain of disorder (P = 0.0996);
MPC		0.72
ClinPred		0.067	T
GERP RS		-2.7
Varity_R		0.57
gMVP		0.74
Mutation Taster		=75/25	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs74719094; hg19: chr14-96768380;