rs10460585

Positions:

• chr2-85328139-T-G

Variant summary

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

The ENST00000398263.6(TGOLN2):​c.-177A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 660,240 control chromosomes in the GnomAD database, including 152,550 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 0.69 (37375 hom., cov: 32)
  • Exomes 𝑓: 0.67 (115175 hom.)
• Consequence: TGOLN2 ENST00000398263.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.501

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGOLN2	ENST00000398263.6	c.-177A>C		5_prime_UTR_variant	1/5	1		A2
	ENST00000703002.1	n.56T>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.694 AC: 105478 AN: 152018 Hom.: 37319 Cov.: 32

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.760

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.960

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.774

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.703

GnomAD4 exome AF: 0.666 AC: 338635 AN: 508102 Hom.: 115175 Cov.: 6 AF XY: 0.669 AC XY: 177698 AN XY: 265606

Gnomad4 AFR exome AF: 0.790

Gnomad4 AMR exome AF: 0.802

Gnomad4 ASJ exome AF: 0.678

Gnomad4 EAS exome AF: 0.951

Gnomad4 SAS exome AF: 0.732

Gnomad4 FIN exome AF: 0.631

Gnomad4 NFE exome AF: 0.614

Gnomad4 OTH exome AF: 0.677

GnomAD4 genome AF: 0.694 AC: 105596 AN: 152138 Hom.: 37375 Cov.: 32 AF XY: 0.699 AC XY: 51993 AN XY: 74358

Gnomad4 AFR AF: 0.787

Gnomad4 AMR AF: 0.760

Gnomad4 ASJ AF: 0.690

Gnomad4 EAS AF: 0.960

Gnomad4 SAS AF: 0.723

Gnomad4 FIN AF: 0.624

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.705

Alfa AF: 0.641 Hom.: 29099

Bravo AF: 0.713

Asia WGS AF: 0.839 AC: 2916 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.3
DANN	Benign	0.59

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: rs10460585; hg19: chr2-85555262;