NM_018036.7:c.6168C>T

Variant names:

• chr14-96285824-G-A
• rs151219519
• NM_018036.7:c.6168C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_018036.7(ATG2B):​c.6168C>T​(p.Gly2056Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00378 in 1,614,096 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0027 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0039 (13 hom.)
• Consequence: ATG2B NM_018036.7 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.04
• Publications: 1 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 14-96285824-G-A is Benign according to our data. Variant chr14-96285824-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1337707.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.04 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 13 AR gene

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.6168C>T	p.Gly2056Gly	synonymous	Exon 42 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.6168C>T	p.Gly2056Gly	synonymous	Exon 42 of 42	ENSP00000353010.4	Q96BY7
	ATG2B	ENST00000938845.1		c.6132C>T	p.Gly2044Gly	synonymous	Exon 42 of 42	ENSP00000608904.1

Frequencies

GnomAD3 genomes AF: 0.00268 AC: 407 AN: 152118 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00374

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00428

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00254 AC: 639 AN: 251440 AF XY: 0.00249

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.00361

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.00419

Gnomad OTH exome AF: 0.00293

GnomAD4 exome AF: 0.00389 AC: 5690 AN: 1461860 Hom.: 13 Cov.: 30 AF XY: 0.00380 AC XY: 2763 AN XY: 727224

African (AFR) AF: 0.000836 AC: 28 AN: 33480

American (AMR) AF: 0.00333 AC: 149 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86258

European-Finnish (FIN) AF: 0.000168 AC: 9 AN: 53420

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5742

European-Non Finnish (NFE) AF: 0.00476 AC: 5295 AN: 1112010

Other (OTH) AF: 0.00326 AC: 197 AN: 60390

GnomAD4 genome AF: 0.00267 AC: 407 AN: 152236 Hom.: 1 Cov.: 33 AF XY: 0.00266 AC XY: 198 AN XY: 74446

African (AFR) AF: 0.00106 AC: 44 AN: 41554

American (AMR) AF: 0.00373 AC: 57 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

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

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10602

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00428 AC: 291 AN: 68016

Other (OTH) AF: 0.00473 AC: 10 AN: 2114

Alfa AF: 0.00279 Hom.: 2

Bravo AF: 0.00274

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00425

EpiControl AF: 0.00516

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	ATG2B-related disorder (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	11
DANN	Benign	0.84
PhyloP100		1.0
Mutation Taster		=92/8	polymorphism

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: rs151219519; hg19: chr14-96752161;