dbSNP rs2292653: TGOLN2:c.1225-140T>C (chr2-85325138-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.362

Publications

10 publications found

Variant links:

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]

TGOLN2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TGOLN2	NM_006464.4 link	c.1225-140T>C	intron_variant	Intron 2 of 3	ENST00000377386.8	NP_006455.2	O43493-2
TGOLN2	NM_001368095.1 link	c.1225-140T>C	intron_variant	Intron 2 of 3		NP_001355024.1
TGOLN2	NM_001368096.1 link	c.1225-140T>C	intron_variant	Intron 2 of 3		NP_001355025.1
TGOLN2	NM_001206844.2 link	c.1051-140T>C	intron_variant	Intron 3 of 4		NP_001193773.1	O43493-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGOLN2	ENST00000377386.8 link	c.1225-140T>C		intron_variant	Intron 2 of 3	1	NM_006464.4	ENSP00000366603.3		O43493-2

Frequencies

GnomAD3 genomes

AF:

0.0933

AC:

14200

AN:

152186

Hom.:

819

Cov.:

show subpopulations

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

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

2212

4425

6637

8850

11062

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

490

980

1470

1960

2450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0933

AC:

14213

AN:

152304

Hom.:

819

Cov.:

AF XY:

0.0971

AC XY:

7232

AN XY:

74460

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0701

AC:

4769

AN:

68032

Other (OTH)

AF:

0.115

AC:

243

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

673

1345

2018

2690

3363

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

154

308

462

616

770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.5

(source)

DANN

Benign

0.86

PhyloP100

0.36

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over