2-85326661-C-T

Variant names:

• chr2-85326661-C-T
• rs1044973
• NM_006464.4:c.1071G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006464.4(TGOLN2):​c.1071G>A​(p.Gly357Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 1,613,792 control chromosomes in the GnomAD database, including 255,151 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. Synonymous variant affecting the same amino acid position (i.e. G357G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.57 (25447 hom., cov: 32)
  • Exomes 𝑓: 0.56 (229704 hom.)
• Consequence: TGOLN2 NM_006464.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 37 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]

ENSG00000307411 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP7: Synonymous conserved (PhyloP=-1.07 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.86 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.1071G>A	p.Gly357Gly	synonymous	Exon 2 of 4	NP_006455.2
	TGOLN2	NM_001368095.1		c.1071G>A	p.Gly357Gly	synonymous	Exon 2 of 4	NP_001355024.1	O43493-7
	TGOLN2	NM_001368096.1		c.1071G>A	p.Gly357Gly	synonymous	Exon 2 of 4	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.1071G>A	p.Gly357Gly	synonymous	Exon 2 of 4	ENSP00000366603.3	O43493-2
	TGOLN2	ENST00000409015.5	TSL:1	c.1071G>A	p.Gly357Gly	synonymous	Exon 2 of 4	ENSP00000387035.1	O43493-7
	TGOLN2	ENST00000409232.7	TSL:1	c.1071G>A	p.Gly357Gly	synonymous	Exon 2 of 4	ENSP00000386443.3	A0A5F9UY30

Frequencies

GnomAD3 genomes AF: 0.573 AC: 87001 AN: 151966 Hom.: 25430 Cov.: 32

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.882

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.739

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.608

GnomAD2 exomes AF: 0.613 AC: 152682 AN: 249266 AF XY: 0.609

Gnomad AFR exome AF: 0.553

Gnomad AMR exome AF: 0.741

Gnomad ASJ exome AF: 0.649

Gnomad EAS exome AF: 0.887

Gnomad FIN exome AF: 0.592

Gnomad NFE exome AF: 0.529

Gnomad OTH exome AF: 0.618

GnomAD4 exome AF: 0.555 AC: 811260 AN: 1461708 Hom.: 229704 Cov.: 88 AF XY: 0.558 AC XY: 405420 AN XY: 727138

African (AFR) AF: 0.554 AC: 18561 AN: 33480

American (AMR) AF: 0.734 AC: 32842 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 16916 AN: 26136

East Asian (EAS) AF: 0.875 AC: 34748 AN: 39700

South Asian (SAS) AF: 0.643 AC: 55435 AN: 86256

European-Finnish (FIN) AF: 0.593 AC: 31660 AN: 53402

Middle Eastern (MID) AF: 0.701 AC: 4042 AN: 5768

European-Non Finnish (NFE) AF: 0.523 AC: 581704 AN: 1111868

Other (OTH) AF: 0.586 AC: 35352 AN: 60374

GnomAD4 genome AF: 0.572 AC: 87054 AN: 152084 Hom.: 25447 Cov.: 32 AF XY: 0.580 AC XY: 43106 AN XY: 74338

African (AFR) AF: 0.545 AC: 22596 AN: 41468

American (AMR) AF: 0.672 AC: 10282 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 2294 AN: 3472

East Asian (EAS) AF: 0.882 AC: 4558 AN: 5170

South Asian (SAS) AF: 0.642 AC: 3100 AN: 4826

European-Finnish (FIN) AF: 0.591 AC: 6252 AN: 10578

Middle Eastern (MID) AF: 0.743 AC: 217 AN: 292

European-Non Finnish (NFE) AF: 0.529 AC: 35977 AN: 67958

Other (OTH) AF: 0.612 AC: 1292 AN: 2112

Alfa AF: 0.554 Hom.: 48931

Bravo AF: 0.581

Asia WGS AF: 0.768 AC: 2669 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	4.6
DANN	Benign	0.87
PhyloP100		-1.1
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.0
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

Other links and lift over

dbSNP: rs1044973; hg19: chr2-85553784; COSMIC: COSV56406254;