chr17-46931204-G-A

Position:

chr17-46931204-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004287.5(GOSR2):c.200G>A(p.Arg67Lys) variant causes a missense change. The variant allele was found at a frequency of 0.343 in 1,435,212 control chromosomes in the GnomAD database, including 85,927 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R67Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.33 ( 8426 hom., cov: 32)

Exomes 𝑓: 0.34 ( 77501 hom. )

Consequence

GOSR2
NM_004287.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:15

Conservation

PhyloP100: 3.76

Variant links:

Genes affected

GOSR2 (HGNC:4431): (golgi SNAP receptor complex member 2) This gene encodes a trafficking membrane protein which transports proteins among the medial- and trans-Golgi compartments. Due to its chromosomal location and trafficking function, this gene may be involved in familial essential hypertension. [provided by RefSeq, Mar 2016]

GOSR2 links:

LRRC37A2 (HGNC:):

LRRC37A2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017098784).

BP6

Variant 17-46931204-G-A is Benign according to our data. Variant chr17-46931204-G-A is described in ClinVar as [Benign]. Clinvar id is 129165.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-46931204-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GOSR2	NM_004287.5 linkuse as main transcript	c.200G>A	p.Arg67Lys	missense_variant	3/6	ENST00000640051.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GOSR2	ENST00000640051.2 linkuse as main transcript	c.200G>A	p.Arg67Lys	missense_variant	3/6	1	NM_004287.5	P3	O14653-1

Frequencies

GnomAD3 genomes

AF:

0.331

AC:

50302

AN:

151950

Hom.:

8433

Cov.:

show subpopulations

Gnomad AFR

AF:

0.296

Gnomad AMI

AF:

0.420

Gnomad AMR

AF:

0.308

Gnomad ASJ

AF:

0.241

Gnomad EAS

AF:

0.385

Gnomad SAS

AF:

0.452

Gnomad FIN

AF:

0.385

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.340

Gnomad OTH

AF:

0.328

GnomAD3 exomes

AF:

0.346

AC:

86785

AN:

250870

Hom.:

15261

AF XY:

0.351

AC XY:

47649

AN XY:

135606

show subpopulations

Gnomad AFR exome

AF:

0.300

Gnomad AMR exome

AF:

0.296

Gnomad ASJ exome

AF:

0.240

Gnomad EAS exome

AF:

0.367

Gnomad SAS exome

AF:

0.427

Gnomad FIN exome

AF:

0.380

Gnomad NFE exome

AF:

0.346

Gnomad OTH exome

AF:

0.329

GnomAD4 exome

AF:

0.345

AC:

442665

AN:

1283142

Hom.:

77501

Cov.:

AF XY:

0.348

AC XY:

225495

AN XY:

647642

show subpopulations

Gnomad4 AFR exome

AF:

0.294

Gnomad4 AMR exome

AF:

0.298

Gnomad4 ASJ exome

AF:

0.242

Gnomad4 EAS exome

AF:

0.411

Gnomad4 SAS exome

AF:

0.428

Gnomad4 FIN exome

AF:

0.378

Gnomad4 NFE exome

AF:

0.341

Gnomad4 OTH exome

AF:

0.329

GnomAD4 genome

AF:

0.331

AC:

50313

AN:

152070

Hom.:

8426

Cov.:

AF XY:

0.335

AC XY:

24863

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.296

Gnomad4 AMR

AF:

0.307

Gnomad4 ASJ

AF:

0.241

Gnomad4 EAS

AF:

0.385

Gnomad4 SAS

AF:

0.450

Gnomad4 FIN

AF:

0.385

Gnomad4 NFE

AF:

0.340

Gnomad4 OTH

AF:

0.329

Alfa

AF:

0.333

Hom.:

21819

Bravo

AF:

0.320

TwinsUK

AF:

0.344

AC:

1275

ALSPAC

AF:

0.345

AC:

1329

ESP6500AA

AF:

0.307

AC:

1354

ESP6500EA

AF:

0.334

AC:

2870

ExAC

AF:

0.349

AC:

42364

Asia WGS

AF:

0.387

AC:

1349

AN:

3478

EpiCase

AF:

0.338

EpiControl

AF:

0.345

ClinVar

Significance: Benign

Submissions summary: Benign:15

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 09, 2014	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 15, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 51% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 47. Only high quality variants are reported. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 19057520) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Progressive myoclonic epilepsy

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

Myoclonic epilepsy, progressive, X-linked

Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 08, 2016

This alteration is classified as 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. -

Progressive myoclonic epilepsy type 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.74

DEOGEN2

Benign

0.027

.;.;.;.;.;.;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.50

T;T;T;T;T;T;T;T;T;T;.;T;T;.;T;T;T;T;T;T;.;T;T

MetaRNN

Benign

0.0017

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.7

.;.;.;N;.;.;N;.;N;.;.;.;.;.;.;.;.;.;.;.;.;.;.

MutationTaster

Benign

1.0

P;P;P;P;P;P

PrimateAI

Uncertain

0.68

PROVEAN

Benign

2.4

.;.;.;N;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.

REVEL

Benign

0.078

Sift

Benign

1.0

.;.;.;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.

Sift4G

Benign

1.0

.;.;.;T;.;.;.;.;.;.;.;T;.;.;.;.;.;.;.;.;.;.;.

Polyphen

0.0

.;.;.;B;.;.;B;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.

Vest4

0.050, 0.11

MPC

0.17

ClinPred

0.0082

GERP RS

4.8

Varity_R

0.12

gMVP

0.25

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