rs139161893

Variant names:

• chr14-96285835-C-A
• rs139161893
• NM_018036.7:c.6157G>T

Your query was ambiguous. Multiple possible variants found:

• chr14-96285835-C-A
• chr14-96285835-C-G
• chr14-96285835-C-T

Variant summary

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

The NM_018036.7(ATG2B):​c.6157G>T​(p.Val2053Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V2053M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ATG2B NM_018036.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.77
• Publications: 0 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: 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_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.6157G>T	p.Val2053Leu	missense	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.6157G>T	p.Val2053Leu	missense	Exon 42 of 42	ENSP00000353010.4	Q96BY7
	ATG2B	ENST00000938845.1		c.6121G>T	p.Val2041Leu	missense	Exon 42 of 42	ENSP00000608904.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461868 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727230

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Uncertain	0.069	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	26
DANN	Benign	0.97
DEOGEN2	Benign	0.0098	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0097	T
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		5.8
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.34
Sift	Benign	0.50	T
Sift4G	Benign	0.44	T
Polyphen		1.0	D
Vest4		0.43
MutPred		0.75		Loss of MoRF binding (P = 0.0847)
MVP		0.52
MPC		0.56
ClinPred		0.84	D
GERP RS		5.8
Varity_R		0.19
gMVP		0.79
Mutation Taster		=69/31	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: rs139161893; hg19: chr14-96752172;