rs2531706

Variant names:

• chr22-20026950-T-C
• rs2531706
• NM_152906.7:c.-40+5704T>C

Variant summary

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

The NM_152906.7(TANGO2):​c.-40+5704T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 152,032 control chromosomes in the GnomAD database, including 22,747 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 0.51 (22747 hom., cov: 32)
• Consequence: TANGO2 NM_152906.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 6 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TANGO2	NM_152906.7	c.-40+5704T>C		intron_variant	Intron 1 of 8	ENST00000327374.9	NP_690870.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TANGO2	ENST00000327374.9	c.-40+5704T>C		intron_variant	Intron 1 of 8	1	NM_152906.7	ENSP00000332721.4

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77731 AN: 151912 Hom.: 22720 Cov.: 32

Gnomad AFR AF: 0.818

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.485

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

GnomAD4 genome AF: 0.512 AC: 77804 AN: 152032 Hom.: 22747 Cov.: 32 AF XY: 0.506 AC XY: 37565 AN XY: 74292

African (AFR) AF: 0.818 AC: 33907 AN: 41462

American (AMR) AF: 0.392 AC: 5988 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1277 AN: 3470

East Asian (EAS) AF: 0.390 AC: 2014 AN: 5164

South Asian (SAS) AF: 0.367 AC: 1769 AN: 4822

European-Finnish (FIN) AF: 0.377 AC: 3978 AN: 10550

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.403 AC: 27417 AN: 67978

Other (OTH) AF: 0.482 AC: 1016 AN: 2110

Alfa AF: 0.464 Hom.: 24724

Bravo AF: 0.530

Asia WGS AF: 0.435 AC: 1518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.4
DANN	Benign	0.53
PhyloP100		-1.2
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: rs2531706; hg19: chr22-20014473; COSMIC: COSV59293050;