Variant 2-108452435-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_181453.4(GCC2):c.185C>G(p.Pro62Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00273 in 1,558,460 control chromosomes in the GnomAD database, including 101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 69 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 32 hom. )

Consequence

GCC2
NM_181453.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.33

Variant links:

Genes affected

GCC2 (HGNC:23218): (GRIP and coiled-coil domain containing 2) The protein encoded by this gene is a peripheral membrane protein localized to the trans-Golgi network. It is sensitive to brefeldin A. This encoded protein contains a GRIP domain which is thought to be used in targeting. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2009]

GCC2 links:

GCC2 (HGNC:):

GCC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015929043).

BP6

Variant 2-108452435-C-G is Benign according to our data. Variant chr2-108452435-C-G is described in ClinVar as [Benign]. Clinvar id is 780830.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GCC2	NM_181453.4 linkuse as main transcript	c.185C>G	p.Pro62Arg	missense_variant	4/23	ENST00000309863.11	NP_852118.2	Q8IWJ2-1B3KR21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GCC2	ENST00000309863.11 linkuse as main transcript	c.185C>G	p.Pro62Arg	missense_variant	4/23	5	NM_181453.4	ENSP00000307939.5		Q8IWJ2-1

Frequencies

GnomAD3 genomes

AF:

0.0159

AC:

2417

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0564

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00340

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00861

GnomAD3 exomes

AF:

0.00404

AC:

1014

AN:

250802

Hom.:

AF XY:

0.00277

AC XY:

376

AN XY:

135594

show subpopulations

Gnomad AFR exome

AF:

0.0575

Gnomad AMR exome

AF:

0.00177

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000984

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000194

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.00130

AC:

1834

AN:

1406274

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

788

AN XY:

702848

show subpopulations

Gnomad4 AFR exome

AF:

0.0461

Gnomad4 AMR exome

AF:

0.00209

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000129

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000744

Gnomad4 OTH exome

AF:

0.00310

GnomAD4 genome

AF:

0.0159

AC:

2421

AN:

152186

Hom.:

Cov.:

AF XY:

0.0151

AC XY:

1127

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0563

Gnomad4 AMR

AF:

0.00340

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00852

Alfa

AF:

0.00260

Hom.:

Bravo

AF:

0.0182

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0572

AC:

252

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00525

AC:

637

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 05, 2018	- -

GCC2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 10, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.067

T;T;T

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.73

T;T;T

MetaRNN

Benign

0.0016

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;.;.

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.7

N;N;N

REVEL

Benign

0.020

Sift

Uncertain

0.0060

D;D;D

Sift4G

Benign

0.41

T;T;T

Polyphen

0.43

B;.;.

Vest4

0.28

MVP

0.18

MPC

0.075

ClinPred

0.010

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.074

gMVP

0.052

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

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

Other links and lift over