22-20036848-CG-TC

Variant names:

• chr22-20036848-CG-TC
• NM_152906.7:c.50_51delCGinsTC
• TANGO2 p.Ala17Val

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_152906.7(TANGO2):​c.50_51delCGinsTC​(p.Ala17Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. A17T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TANGO2 NM_152906.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.63
• Publications: 0 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: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152906.7. 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
	TANGO2	NM_152906.7	MANE Select	c.50_51delCGinsTC	p.Ala17Val	missense	N/A	NP_690870.3
	TANGO2	NM_001322142.2		c.50_51delCGinsTC	p.Ala17Val	missense	N/A	NP_001309071.1
	TANGO2	NM_001283106.3		c.50_51delCGinsTC	p.Ala17Val	missense	N/A	NP_001270035.1	Q6ICL3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TANGO2	ENST00000327374.9	TSL:1 MANE Select	c.50_51delCGinsTC	p.Ala17Val	missense	N/A	ENSP00000332721.4	Q6ICL3-1
	TANGO2	ENST00000852305.1		c.50_51delCGinsTC	p.Ala17Val	missense	N/A	ENSP00000522364.1
	TANGO2	ENST00000852310.1		c.50_51delCGinsTC	p.Ala17Val	missense	N/A	ENSP00000522369.1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr22-20024371;