14-96289988-A-G

Variant names:

• chr14-96289988-A-G
• rs114552965
• NM_018036.7:c.5857-183T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018036.7(ATG2B):​c.5857-183T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 722,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ATG2B NM_018036.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

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.5857-183T>C		intron	N/A	NP_060506.6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG2B	ENST00000359933.6	TSL:5 MANE Select	c.5857-183T>C		intron	N/A	ENSP00000353010.4	Q96BY7
	ATG2B	ENST00000938845.1		c.5821-183T>C		intron	N/A	ENSP00000608904.1
	ATG2B	ENST00000555263.1	TSL:2	n.143-183T>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 1 AN: 722080 Hom.: 0 AF XY: 0.00000275 AC XY: 1 AN XY: 363470

African (AFR) AF: 0.00 AC: 0 AN: 17356

American (AMR) AF: 0.00 AC: 0 AN: 16730

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14452

East Asian (EAS) AF: 0.00 AC: 0 AN: 29184

South Asian (SAS) AF: 0.00 AC: 0 AN: 47002

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25890

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3632

European-Non Finnish (NFE) AF: 0.00000187 AC: 1 AN: 533926

Other (OTH) AF: 0.00 AC: 0 AN: 33908

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.9
DANN	Benign	0.68
PhyloP100		1.5

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: rs114552965; hg19: chr14-96756325;