chr17-46931204-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 14/21 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

Publications

80 publications found

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:

ENSG00000262633 (HGNC:):

ENSG00000262633 links:

LRRC37A2 (HGNC:32404): (leucine rich repeat containing 37 member A2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRRC37A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 129165.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
GOSR2	NM_004287.5 link	c.200G>A	p.Arg67Lys	missense_variant	Exon 3 of 6	ENST00000640051.2	NP_004278.2	O14653-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOSR2	ENST00000640051.2 link	c.200G>A	p.Arg67Lys	missense_variant	Exon 3 of 6	1	NM_004287.5	ENSP00000492751.1		O14653-1
ENSG00000262633	ENST00000571841.1 link	n.200G>A		non_coding_transcript_exon_variant	Exon 3 of 10	5		ENSP00000461460.1		E7EQ34

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

GnomAD2 exomes

AF:

0.346

AC:

86785

AN:

250870

AF XY:

0.351

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 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

African (AFR)

AF:

0.294

AC:

8858

AN:

30120

American (AMR)

AF:

0.298

AC:

13261

AN:

44492

Ashkenazi Jewish (ASJ)

AF:

0.242

AC:

6072

AN:

25096

East Asian (EAS)

AF:

0.411

AC:

15973

AN:

38874

South Asian (SAS)

AF:

0.428

AC:

35292

AN:

82534

European-Finnish (FIN)

AF:

0.378

AC:

20175

AN:

53342

Middle Eastern (MID)

AF:

0.275

AC:

1497

AN:

5448

European-Non Finnish (NFE)

AF:

0.341

AC:

323641

AN:

948862

Other (OTH)

AF:

0.329

AC:

17896

AN:

54374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

13081

26163

39244

52326

65407

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9728

19456

29184

38912

48640

<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:

0.331

AC:

50313

AN:

152070

Hom.:

8426

Cov.:

AF XY:

0.335

AC XY:

24863

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.296

AC:

12293

AN:

41476

American (AMR)

AF:

0.307

AC:

4704

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.241

AC:

834

AN:

3466

East Asian (EAS)

AF:

0.385

AC:

1991

AN:

5166

South Asian (SAS)

AF:

0.450

AC:

2172

AN:

4826

European-Finnish (FIN)

AF:

0.385

AC:

4059

AN:

10548

Middle Eastern (MID)

AF:

0.310

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.340

AC:

23092

AN:

67976

Other (OTH)

AF:

0.329

AC:

694

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1742

3484

5226

6968

8710

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

510

1020

1530

2040

2550

<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:

0.334

Hom.:

43667

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

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 09, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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. -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 19057520) -

Apr 20, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Progressive myoclonic epilepsy

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Myoclonic epilepsy, progressive, X-linked

Benign:1

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Jan 08, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

(source)

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;.;.;.;.;.;.;.;.;.;.;.;.;.;.

PhyloP100

3.8

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

PromoterAI

0.048

Neutral

(source)

Varity_R

0.12

gMVP

0.25

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over