chr17-46923196-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_004287.5(GOSR2):c.4G>A(p.Asp2Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000043 in 1,394,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D2G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

GOSR2
NM_004287.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.75

Publications

1 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:

GOSR2-DT (HGNC:55346): (GOSR2 divergent transcript)

GOSR2-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.41326144).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004287.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GOSR2	NM_004287.5	MANE Select	c.4G>A	p.Asp2Asn	missense	Exon 1 of 6	NP_004278.2
GOSR2	NM_001321133.2		c.4G>A	p.Asp2Asn	missense	Exon 1 of 7	NP_001308062.1	I3NI02
GOSR2	NM_054022.4		c.4G>A	p.Asp2Asn	missense	Exon 1 of 7	NP_473363.1	O14653-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GOSR2	ENST00000640051.2	TSL:1 MANE Select	c.4G>A	p.Asp2Asn	missense	Exon 1 of 6	ENSP00000492751.1	O14653-1
GOSR2	ENST00000225567.9	TSL:1	c.4G>A	p.Asp2Asn	missense	Exon 1 of 7	ENSP00000225567.4	O14653-2
GOSR2	ENST00000640621.1	TSL:1	c.4G>A	p.Asp2Asn	missense	Exon 1 of 5	ENSP00000492830.1	O14653-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000648

AC:

AN:

154336

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000119

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000430

AC:

AN:

1394944

Hom.:

Cov.:

AF XY:

0.00000291

AC XY:

AN XY:

688320

show subpopulations

African (AFR)

AF:

0.0000317

AC:

AN:

31520

American (AMR)

AF:

0.00

AC:

AN:

35696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25122

East Asian (EAS)

AF:

0.00

AC:

AN:

35708

South Asian (SAS)

AF:

0.00

AC:

AN:

79144

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49132

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5664

European-Non Finnish (NFE)

AF:

0.00000465

AC:

AN:

1075124

Other (OTH)

AF:

0.00

AC:

AN:

57834

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Progressive myoclonic epilepsy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.029

Eigen

Benign

-0.16

Eigen_PC

Benign

0.0017

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.40

M_CAP

Benign

0.024

MetaRNN

Benign

0.41

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.46

PhyloP100

4.7

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.7

REVEL

Benign

0.11

Sift

Benign

0.044

Sift4G

Uncertain

0.0040

Polyphen

0.046

Vest4

0.31

MutPred

0.57

Gain of MoRF binding (P = 0.1491)

MVP

0.70

MPC

0.17

ClinPred

0.69

GERP RS

5.0

PromoterAI

-0.15

Neutral

(source)

Varity_R

0.25

gMVP

0.10

Mutation Taster

=83/17

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over