14-96289988-A-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018036.7(ATG2B):​c.5857-183T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00539 in 874,338 control chromosomes in the GnomAD database, including 170 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (122 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (48 hom.)
• Consequence: ATG2B NM_018036.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.49

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 14-96289988-A-T is Benign according to our data. Variant chr14-96289988-A-T is described in ClinVar as [Benign]. Clinvar id is 1230270.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG2B	NM_018036.7	c.5857-183T>A		intron_variant	Intron 40 of 41	ENST00000359933.6	NP_060506.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG2B	ENST00000359933.6	c.5857-183T>A		intron_variant	Intron 40 of 41	5	NM_018036.7	ENSP00000353010.4
ATG2B	ENST00000555263.1	n.143-183T>A		intron_variant	Intron 1 of 1	2
ATG2B	ENST00000261834.9	n.*148T>A		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0213 AC: 3238 AN: 152158 Hom.: 122 Cov.: 32

Gnomad AFR AF: 0.0735

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0102

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.0143

GnomAD4 exome AF: 0.00203 AC: 1469 AN: 722062 Hom.: 48 AF XY: 0.00175 AC XY: 636 AN XY: 363464

Gnomad4 AFR exome AF: 0.0654

Gnomad4 AMR exome AF: 0.00640

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000213

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000974

Gnomad4 OTH exome AF: 0.00493

GnomAD4 genome AF: 0.0213 AC: 3242 AN: 152276 Hom.: 122 Cov.: 32 AF XY: 0.0198 AC XY: 1471 AN XY: 74476

Gnomad4 AFR AF: 0.0734

Gnomad4 AMR AF: 0.0101

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.0156 Hom.: 6

Bravo AF: 0.0241

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.6
DANN	Benign	0.76

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

LitVar

Other links and lift over

dbSNP: rs114552965; hg19: chr14-96756325;