17-46929530-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_004287.5(GOSR2):c.40G>A(p.Glu14Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000414 in 1,549,904 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 3 hom. )

Consequence

GOSR2
NM_004287.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: 7.75

Publications

4 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008037865).

BP6

Variant 17-46929530-G-A is Benign according to our data. Variant chr17-46929530-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 205627.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00214 (325/152220) while in subpopulation AFR AF = 0.00758 (315/41538). AF 95% confidence interval is 0.00689. There are 0 homozygotes in GnomAd4. There are 149 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 3 AR,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOSR2	NM_004287.5 link	c.40G>A	p.Glu14Lys	missense_variant	Exon 2 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.40G>A	p.Glu14Lys	missense_variant	Exon 2 of 6	1	NM_004287.5	ENSP00000492751.1		O14653-1
ENSG00000262633	ENST00000571841.1 link	n.40G>A		non_coding_transcript_exon_variant	Exon 2 of 10	5		ENSP00000461460.1		E7EQ34

Frequencies

GnomAD3 genomes

AF:

0.00213

AC:

324

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00758

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000514

AC:

129

AN:

251084

AF XY:

0.000368

show subpopulations

Gnomad AFR exome

AF:

0.00708

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000226

AC:

316

AN:

1397684

Hom.:

Cov.:

AF XY:

0.000179

AC XY:

125

AN XY:

699456

show subpopulations

African (AFR)

AF:

0.00782

AC:

252

AN:

32220

American (AMR)

AF:

0.000202

AC:

AN:

44658

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25742

East Asian (EAS)

AF:

0.00

AC:

AN:

39388

South Asian (SAS)

AF:

0.000106

AC:

AN:

85054

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53142

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5662

European-Non Finnish (NFE)

AF:

0.0000114

AC:

AN:

1053620

Other (OTH)

AF:

0.000584

AC:

AN:

58198

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00214

AC:

325

AN:

152220

Hom.:

Cov.:

AF XY:

0.00200

AC XY:

149

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.00758

AC:

315

AN:

41538

American (AMR)

AF:

0.000327

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68002

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000667

Hom.:

Bravo

AF:

0.00255

ESP6500AA

AF:

0.00817

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000576

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:5

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 23, 2014

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Aug 09, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Progressive myoclonic epilepsy

Uncertain:1Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Aug 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.12

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

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.89

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.0080

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

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.3

.;.;.;M;.;.;M;.;M;.;.;.;.;.;.

PhyloP100

7.8

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-3.0

.;.;.;D;D;.;.;.;.;.;.;.;.;.;.

REVEL

Benign

0.20

Sift

Uncertain

0.0040

.;.;.;D;T;.;.;.;.;.;.;.;.;.;.

Sift4G

Benign

0.092

.;.;.;T;D;T;.;.;.;.;T;.;.;.;.

Polyphen

1.0, 0.97

.;.;.;D;.;.;D;.;.;.;.;.;.;.;.

Vest4

0.79, 0.77, 0.77, 0.75

MVP

0.51

MPC

0.25

ClinPred

0.068

GERP RS

4.8

PromoterAI

0.033

Neutral

(source)

Varity_R

0.58

gMVP

0.37

Mutation Taster

=98/2

polymorphism

(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