rs2292653

chr2-85325138-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006464.4(TGOLN2):c.1225-140T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0898 in 711,544 control chromosomes in the GnomAD database, including 4,065 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 0.093 (819 hom., cov: 33)
  • Exomes 𝑓: 0.089 (3246 hom.)
• Consequence: TGOLN2 NM_006464.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.362

Genes affected

TGOLN2 (HGNC:15450): (trans-golgi network protein 2) This gene encodes a type I integral membrane protein that is localized to the trans-Golgi network, a major sorting station for secretory and membrane proteins. The encoded protein cycles between early endosomes and the trans-Golgi network, and may play a role in exocytic vesicle formation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGOLN2	NM_006464.4	c.1225-140T>C		intron_variant		ENST00000377386.8
TGOLN2	NM_001206844.2	c.1051-140T>C		intron_variant
TGOLN2	NM_001368095.1	c.1225-140T>C		intron_variant
TGOLN2	NM_001368096.1	c.1225-140T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGOLN2	ENST00000377386.8	c.1225-140T>C		intron_variant		1	NM_006464.4	A2

Frequencies

GnomAD3 genomes AF: 0.0933 AC: 14200 AN: 152186 Hom.: 819 Cov.: 33

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0744

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.0656

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0701

Gnomad OTH AF: 0.112

GnomAD4 exome AF: 0.0889 AC: 49692 AN: 559240 Hom.: 3246 AF XY: 0.0872 AC XY: 25514 AN XY: 292548

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.0631

Gnomad4 ASJ exome AF: 0.101

Gnomad4 EAS exome AF: 0.305

Gnomad4 SAS exome AF: 0.0650

Gnomad4 FIN exome AF: 0.108

Gnomad4 NFE exome AF: 0.0710

Gnomad4 OTH exome AF: 0.0952

GnomAD4 genome AF: 0.0933 AC: 14213 AN: 152304 Hom.: 819 Cov.: 33 AF XY: 0.0971 AC XY: 7232 AN XY: 74460

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.0743

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.296

Gnomad4 SAS AF: 0.0648

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.0701

Gnomad4 OTH AF: 0.115

Alfa AF: 0.0749 Hom.: 679

Bravo AF: 0.0935

Asia WGS AF: 0.163 AC: 568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	7.5
Dann	Benign	0.86

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

LitVar

Other links and lift over

dbSNP: rs2292653; hg19: chr2-85552261;