rs2292653

Variant names:

• chr2-85325138-A-G
• rs2292653
• NM_006464.4:c.1225-140T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006464.4. 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
	TGOLN2	NM_006464.4	MANE Select	c.1225-140T>C		intron	N/A	NP_006455.2
	TGOLN2	NM_001368095.1		c.1225-140T>C		intron	N/A	NP_001355024.1	O43493-7
	TGOLN2	NM_001368096.1		c.1225-140T>C		intron	N/A	NP_001355025.1	A0A5F9UY30

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGOLN2	ENST00000377386.8	TSL:1 MANE Select	c.1225-140T>C		intron	N/A	ENSP00000366603.3	O43493-2
	TGOLN2	ENST00000409015.5	TSL:1	c.1225-140T>C		intron	N/A	ENSP00000387035.1	O43493-7
	TGOLN2	ENST00000409232.7	TSL:1	c.1225-140T>C		intron	N/A	ENSP00000386443.3	A0A5F9UY30

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

African (AFR) AF: 0.104 AC: 1519 AN: 14548

American (AMR) AF: 0.0631 AC: 1328 AN: 21050

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 1527 AN: 15076

East Asian (EAS) AF: 0.305 AC: 9716 AN: 31842

South Asian (SAS) AF: 0.0650 AC: 3185 AN: 48994

European-Finnish (FIN) AF: 0.108 AC: 3497 AN: 32302

Middle Eastern (MID) AF: 0.121 AC: 337 AN: 2792

European-Non Finnish (NFE) AF: 0.0710 AC: 25741 AN: 362770

Other (OTH) AF: 0.0952 AC: 2842 AN: 29866

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

African (AFR) AF: 0.106 AC: 4389 AN: 41568

American (AMR) AF: 0.0743 AC: 1136 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 376 AN: 3470

East Asian (EAS) AF: 0.296 AC: 1535 AN: 5188

South Asian (SAS) AF: 0.0648 AC: 313 AN: 4830

European-Finnish (FIN) AF: 0.124 AC: 1315 AN: 10602

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.0701 AC: 4769 AN: 68032

Other (OTH) AF: 0.115 AC: 243 AN: 2114

Alfa AF: 0.0763 Hom.: 979

Bravo AF: 0.0935

Asia WGS AF: 0.163 AC: 568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.5
DANN	Benign	0.86
PhyloP100		0.36
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

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

Other links and lift over

dbSNP: rs2292653;

hg19: chr2-85552261;