Variant 17-46923197-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004287.5(GOSR2):c.5A>C(p.Asp2Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000388 in 1,547,378 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

GOSR2
NM_004287.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.43

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GOSR2	NM_004287.5 linkuse as main transcript	c.5A>C	p.Asp2Ala	missense_variant	1/6	ENST00000640051.2	NP_004278.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GOSR2	ENST00000640051.2 linkuse as main transcript	c.5A>C	p.Asp2Ala	missense_variant	1/6	1	NM_004287.5	ENSP00000492751	P3	O14653-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000358

AC:

AN:

1395214

Hom.:

Cov.:

AF XY:

0.00000436

AC XY:

AN XY:

688460

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000465

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

Nov 08, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.047

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.14

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

Eigen

Benign

-0.063

Eigen_PC

Benign

0.056

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.24

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

M_CAP

Benign

0.054

MetaRNN

Uncertain

0.54

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

MetaSVM

Benign

-0.81

MutationAssessor

Benign

0.81

.;.;.;L;.;.;L;.;L;.;.;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-3.3

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

REVEL

Benign

0.16

Sift

Uncertain

0.0040

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

Sift4G

Uncertain

0.0090

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

Polyphen

0.38, 0.12

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

Vest4

0.33, 0.35, 0.29, 0.34

MutPred

0.59

Gain of catalytic residue at D2 (P = 0.045);Gain of catalytic residue at D2 (P = 0.045);Gain of catalytic residue at D2 (P = 0.045);Gain of catalytic residue at D2 (P = 0.045);Gain of catalytic residue at D2 (P = 0.045);Gain of catalytic residue at D2 (P = 0.045);Gain of catalytic residue at D2 (P = 0.045);Gain of catalytic residue at D2 (P = 0.045);Gain of catalytic residue at D2 (P = 0.045);Gain of catalytic residue at D2 (P = 0.045);Gain of catalytic residue at D2 (P = 0.045);Gain of catalytic residue at D2 (P = 0.045);Gain of catalytic residue at D2 (P = 0.045);Gain of catalytic residue at D2 (P = 0.045);

MVP

0.76

MPC

0.38

ClinPred

0.97

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.47

gMVP

0.23

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

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

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