22-20036651-A-G

Variant summary

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

The NM_152906.7(TANGO2):c.-39-109A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.975 in 918,516 control chromosomes in the GnomAD database, including 437,111 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.98 (73034 hom., cov: 32)
  • Exomes 𝑓: 0.97 (364077 hom.)
• Consequence: TANGO2 NM_152906.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.564

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 22-20036651-A-G is Benign according to our data. Variant chr22-20036651-A-G is described in ClinVar as [Benign]. Clinvar id is 684137.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.986 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TANGO2	NM_152906.7	c.-39-109A>G		intron_variant		ENST00000327374.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TANGO2	ENST00000327374.9	c.-39-109A>G		intron_variant		1	NM_152906.7	P1

Frequencies

GnomAD3 genomes AF: 0.979 AC: 148997 AN: 152156 Hom.: 72976 Cov.: 32

Gnomad AFR AF: 0.994

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.970

Gnomad ASJ AF: 0.983

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.984

Gnomad FIN AF: 0.947

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.975

Gnomad OTH AF: 0.983

GnomAD4 exome AF: 0.975 AC: 746874 AN: 766242 Hom.: 364077 AF XY: 0.975 AC XY: 388646 AN XY: 398572

Gnomad4 AFR exome AF: 0.995

Gnomad4 AMR exome AF: 0.961

Gnomad4 ASJ exome AF: 0.982

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.982

Gnomad4 FIN exome AF: 0.952

Gnomad4 NFE exome AF: 0.974

Gnomad4 OTH exome AF: 0.975

GnomAD4 genome AF: 0.979 AC: 149113 AN: 152274 Hom.: 73034 Cov.: 32 AF XY: 0.978 AC XY: 72780 AN XY: 74450

Gnomad4 AFR AF: 0.994

Gnomad4 AMR AF: 0.970

Gnomad4 ASJ AF: 0.983

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.984

Gnomad4 FIN AF: 0.947

Gnomad4 NFE AF: 0.975

Gnomad4 OTH AF: 0.983

Alfa AF: 0.972 Hom.: 8517

Bravo AF: 0.981

Asia WGS AF: 0.990 AC: 3443 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.60
Dann	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2531713; hg19: chr22-20024174;