chr2-85322748-G-A

Position:

chr2-85322748-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The ENST00000409015.5(TGOLN2):c.1360C>T(p.Pro454Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000106 in 1,611,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

TGOLN2
ENST00000409015.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.790

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 made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06533888).

BP6

Variant 2-85322748-G-A is Benign according to our data. Variant chr2-85322748-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3176784.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TGOLN2	NM_006464.4 linkuse as main transcript	c.1309-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000377386.8	NP_006455.2
TGOLN2	NM_001368095.1 linkuse as main transcript	c.1360C>T	p.Pro454Ser	missense_variant	4/4		NP_001355024.1
TGOLN2	NM_001368096.1 linkuse as main transcript	c.1319C>T	p.Pro440Leu	missense_variant	4/4		NP_001355025.1
TGOLN2	NM_001206844.2 linkuse as main transcript	c.1135-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_001193773.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGOLN2	ENST00000409015.5 linkuse as main transcript	c.1360C>T	p.Pro454Ser	missense_variant	4/4	1		ENSP00000387035	P5	O43493-7
TGOLN2	ENST00000409232.7 linkuse as main transcript	c.1319C>T	p.Pro440Leu	missense_variant	4/4	1		ENSP00000386443	A2
TGOLN2	ENST00000377386.8 linkuse as main transcript	c.1309-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_006464.4	ENSP00000366603	A2	O43493-2
TGOLN2	ENST00000398263.6 linkuse as main transcript	c.1135-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000381312	A2	O43493-4

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000122

AC:

AN:

245448

Hom.:

AF XY:

0.00000749

AC XY:

AN XY:

133432

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000268

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1458934

Hom.:

Cov.:

AF XY:

0.00000827

AC XY:

AN XY:

725746

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152094

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000675

Hom.:

Bravo

AF:

0.0000189

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 22, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.33

DANN

Benign

0.31

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.018

M_CAP

Benign

0.00092

MetaRNN

Benign

0.065

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N;N

PROVEAN

Benign

0.22

REVEL

Benign

0.041

Sift

Uncertain

0.015

Sift4G

Benign

0.85

Vest4

0.22

MutPred

0.39

Loss of disorder (P = 0.0149);

MVP

0.014

ClinPred

0.055

GERP RS

-8.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

gMVP

0.097

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over