chr14-96285835-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 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

Scores

1
7
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.77
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ATG2BNM_018036.7 linkc.6157G>T p.Val2053Leu missense_variant Exon 42 of 42 ENST00000359933.6 NP_060506.6 Q96BY7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ATG2BENST00000359933.6 linkc.6157G>T p.Val2053Leu missense_variant Exon 42 of 42 5 NM_018036.7 ENSP00000353010.4 Q96BY7

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
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-96752172; API