rs399162

Variant names:

• chr22-20059164-G-A
• rs399162
• NM_152906.7:c.452-2366G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152906.7(TANGO2):​c.452-2366G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 152,040 control chromosomes in the GnomAD database, including 30,562 homozygotes. 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: 𝑓 0.63 (30562 hom., cov: 32)
• Consequence: TANGO2 NM_152906.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09
• Publications: 5 publications found

Genes affected

TANGO2 (HGNC:25439): (transport and golgi organization 2 homolog) This gene belongs to the transport and Golgi organization family, whose members are predicted to play roles in secretory protein loading in the endoplasmic reticulum. Depletion of this gene in Drosophila S2 cells causes fusion of the Golgi with the ER. In mouse tissue culture cells, this protein co-localizes with a mitochondrially targeted mCherry protein and displays very low levels of co-localization with Golgi and peroxisomes. Allelic variants of this gene are associated with rhabdomyolysis, metabolic crises with encephalopathy, and cardiac arrhythmia. [provided by RefSeq, Apr 2016]

TANGO2 Gene-Disease associations (from GenCC):

• recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ENSG00000236540 (HGNC:41096):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TANGO2	NM_152906.7	c.452-2366G>A		intron_variant	Intron 6 of 8	ENST00000327374.9	NP_690870.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TANGO2	ENST00000327374.9	c.452-2366G>A		intron_variant	Intron 6 of 8	1	NM_152906.7	ENSP00000332721.4

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95365 AN: 151922 Hom.: 30535 Cov.: 32

Gnomad AFR AF: 0.692

Gnomad AMI AF: 0.550

Gnomad AMR AF: 0.711

Gnomad ASJ AF: 0.604

Gnomad EAS AF: 0.863

Gnomad SAS AF: 0.678

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.639

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.628 AC: 95446 AN: 152040 Hom.: 30562 Cov.: 32 AF XY: 0.631 AC XY: 46934 AN XY: 74330

African (AFR) AF: 0.692 AC: 28698 AN: 41444

American (AMR) AF: 0.711 AC: 10868 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 2093 AN: 3468

East Asian (EAS) AF: 0.862 AC: 4462 AN: 5176

South Asian (SAS) AF: 0.677 AC: 3266 AN: 4822

European-Finnish (FIN) AF: 0.523 AC: 5523 AN: 10562

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.567 AC: 38507 AN: 67966

Other (OTH) AF: 0.638 AC: 1348 AN: 2112

Alfa AF: 0.596 Hom.: 46310

Bravo AF: 0.646

Asia WGS AF: 0.730 AC: 2539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.61
DANN	Benign	0.43
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs399162; hg19: chr22-20046687;