Genetic Variant NM_152906.7:c.-40+6247C>T (chr22-20027493-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_152906.7(TANGO2):c.-40+6247C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 152,064 control chromosomes in the GnomAD database, including 12,100 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 0.39 ( 12100 hom., cov: 33)

Consequence

TANGO2
NM_152906.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.109

Publications

5 publications found

Variant links:

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

TANGO2 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TANGO2	NM_152906.7 link	c.-40+6247C>T		intron_variant	Intron 1 of 8	ENST00000327374.9	NP_690870.3	Q6ICL3-1B7Z4V5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TANGO2	ENST00000327374.9 link	c.-40+6247C>T		intron_variant	Intron 1 of 8	1	NM_152906.7	ENSP00000332721.4		Q6ICL3-1

Frequencies

GnomAD3 genomes

AF:

0.393

AC:

59733

AN:

151946

Hom.:

12107

Cov.:

show subpopulations

Gnomad AFR

AF:

0.489

Gnomad AMI

AF:

0.247

Gnomad AMR

AF:

0.316

Gnomad ASJ

AF:

0.306

Gnomad EAS

AF:

0.303

Gnomad SAS

AF:

0.277

Gnomad FIN

AF:

0.337

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.383

Gnomad OTH

AF:

0.386

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

GnomAD4 genome

AF:

0.393

AC:

59748

AN:

152064

Hom.:

12100

Cov.:

AF XY:

0.388

AC XY:

28814

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.488

AC:

20248

AN:

41470

American (AMR)

AF:

0.316

AC:

4823

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.306

AC:

1060

AN:

3468

East Asian (EAS)

AF:

0.302

AC:

1565

AN:

5174

South Asian (SAS)

AF:

0.277

AC:

1337

AN:

4820

European-Finnish (FIN)

AF:

0.337

AC:

3564

AN:

10568

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.383

AC:

26016

AN:

67980

Other (OTH)

AF:

0.383

AC:

808

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1846

3693

5539

7386

9232

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

564

1128

1692

2256

2820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.386

Hom.:

44391

Bravo

AF:

0.400

Asia WGS

AF:

0.325

AC:

1132

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

2.0

(source)

DANN

Benign

0.46

PhyloP100

-0.11

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over