Genetic Variant GOSR2:p.Asp2Val (chr17-46923197-A-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004287.5(GOSR2):c.5A>T(p.Asp2Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000043 in 1,395,214 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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

Not reported in ClinVar

Conservation

PhyloP100: 4.43

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.5A>T	p.Asp2Val	missense	Exon 1 of 6	NP_004278.2
GOSR2	NM_001321133.2		c.5A>T	p.Asp2Val	missense	Exon 1 of 7	NP_001308062.1	I3NI02
GOSR2	NM_054022.4		c.5A>T	p.Asp2Val	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.5A>T	p.Asp2Val	missense	Exon 1 of 6	ENSP00000492751.1	O14653-1
GOSR2	ENST00000225567.9	TSL:1	c.5A>T	p.Asp2Val	missense	Exon 1 of 7	ENSP00000225567.4	O14653-2
GOSR2	ENST00000640621.1	TSL:1	c.5A>T	p.Asp2Val	missense	Exon 1 of 5	ENSP00000492830.1	O14653-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000648

AC:

AN:

154370

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000169

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000430

AC:

AN:

1395214

Hom.:

Cov.:

AF XY:

0.00000436

AC XY:

AN XY:

688460

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31532

American (AMR)

AF:

0.00

AC:

AN:

35696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25126

East Asian (EAS)

AF:

0.00

AC:

AN:

35710

South Asian (SAS)

AF:

0.00

AC:

AN:

79148

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49154

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5664

European-Non Finnish (NFE)

AF:

0.00000558

AC:

AN:

1075350

Other (OTH)

AF:

0.00

AC:

AN:

57834

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

0.0040

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

Eigen

Benign

0.12

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.39

M_CAP

Uncertain

0.10

MetaRNN

Uncertain

0.59

MetaSVM

Benign

-0.59

MutationAssessor

Benign

0.81

PhyloP100

4.4

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-4.2

REVEL

Benign

0.26

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

0.81

Vest4

0.45

MutPred

0.55

Loss of disorder (P = 0.0823)

MVP

0.79

MPC

0.64

ClinPred

0.99

GERP RS

5.0

PromoterAI

-0.081

Neutral

(source)

Varity_R

0.67

gMVP

0.30

Mutation Taster

=75/25

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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