2-85321516-A-G

Position:

• chr2-85321516-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.*1220T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 152,552 control chromosomes in the GnomAD database, including 36,822 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 (36734 hom., cov: 32)
  • Exomes 𝑓: 0.65 (88 hom.)
• Consequence: TGOLN2 NM_006464.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.308

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGOLN2	NM_006464.4	c.*1220T>C		3_prime_UTR_variant	4/4	ENST00000377386.8	NP_006455.2
TGOLN2	NM_001206844.2	c.*1220T>C		3_prime_UTR_variant	5/5		NP_001193773.1
TGOLN2	NM_001368095.1	c.*1227T>C		3_prime_UTR_variant	4/4		NP_001355024.1
TGOLN2	NM_001368096.1	c.*1189T>C		3_prime_UTR_variant	4/4		NP_001355025.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGOLN2	ENST00000377386.8	c.*1220T>C		3_prime_UTR_variant	4/4	1	NM_006464.4	ENSP00000366603	A2
TGOLN2	ENST00000398263.6	c.*1220T>C		3_prime_UTR_variant	5/5	1		ENSP00000381312	A2

Frequencies

GnomAD3 genomes AF: 0.686 AC: 104296 AN: 151998 Hom.: 36674 Cov.: 32

Gnomad AFR AF: 0.799

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.750

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.960

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.692

GnomAD4 exome AF: 0.647 AC: 281 AN: 434 Hom.: 88 Cov.: 0 AF XY: 0.650 AC XY: 169 AN XY: 260

Gnomad4 FIN exome AF: 0.651

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.686 AC: 104418 AN: 152118 Hom.: 36734 Cov.: 32 AF XY: 0.691 AC XY: 51365 AN XY: 74348

Gnomad4 AFR AF: 0.800

Gnomad4 AMR AF: 0.750

Gnomad4 ASJ AF: 0.688

Gnomad4 EAS AF: 0.960

Gnomad4 SAS AF: 0.697

Gnomad4 FIN AF: 0.611

Gnomad4 NFE AF: 0.594

Gnomad4 OTH AF: 0.695

Alfa AF: 0.628 Hom.: 30524

Bravo AF: 0.706

Asia WGS AF: 0.828 AC: 2877 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.1
DANN	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs6547611; hg19: chr2-85548639;