dbSNP rs61729897: GCC2:p.Glu343Glu (chr2-108470358-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_181453.4(GCC2):c.1029A>G(p.Glu343Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00597 in 1,605,726 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0044 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0061 ( 55 hom. )

Consequence

GCC2
NM_181453.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.667

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 2-108470358-A-G is Benign according to our data. Variant chr2-108470358-A-G is described in ClinVar as [Benign]. Clinvar id is 774289.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.667 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00613 (8914/1453386) while in subpopulation EAS AF= 0.0203 (803/39580). AF 95% confidence interval is 0.0191. There are 55 homozygotes in gnomad4_exome. There are 4516 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCC2	NM_181453.4 link	c.1029A>G	p.Glu343Glu	synonymous_variant	Exon 6 of 23	ENST00000309863.11	NP_852118.2	Q8IWJ2-1B3KR21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCC2	ENST00000309863.11 link	c.1029A>G	p.Glu343Glu	synonymous_variant	Exon 6 of 23	5	NM_181453.4	ENSP00000307939.5		Q8IWJ2-1

Frequencies

GnomAD3 genomes

AF:

0.00440

AC:

670

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00517

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.0112

Gnomad SAS

AF:

0.0130

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00548

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00599

AC:

1464

AN:

244580

Hom.:

AF XY:

0.00611

AC XY:

809

AN XY:

132330

show subpopulations

Gnomad AFR exome

AF:

0.00127

Gnomad AMR exome

AF:

0.00465

Gnomad ASJ exome

AF:

0.00556

Gnomad EAS exome

AF:

0.0149

Gnomad SAS exome

AF:

0.0117

Gnomad FIN exome

AF:

0.000512

Gnomad NFE exome

AF:

0.00519

Gnomad OTH exome

AF:

0.00659

GnomAD4 exome

AF:

0.00613

AC:

8914

AN:

1453386

Hom.:

Cov.:

AF XY:

0.00625

AC XY:

4516

AN XY:

723114

show subpopulations

Gnomad4 AFR exome

AF:

0.000999

Gnomad4 AMR exome

AF:

0.00467

Gnomad4 ASJ exome

AF:

0.00479

Gnomad4 EAS exome

AF:

0.0203

Gnomad4 SAS exome

AF:

0.0124

Gnomad4 FIN exome

AF:

0.000863

Gnomad4 NFE exome

AF:

0.00568

Gnomad4 OTH exome

AF:

0.00565

GnomAD4 genome

AF:

0.00441

AC:

672

AN:

152340

Hom.:

Cov.:

AF XY:

0.00458

AC XY:

341

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.00113

Gnomad4 AMR

AF:

0.00516

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.0112

Gnomad4 SAS

AF:

0.0135

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00548

Gnomad4 OTH

AF:

0.00994

Alfa

AF:

0.00486

Hom.:

Bravo

AF:

0.00458

Asia WGS

AF:

0.0140

AC:

AN:

3474

EpiCase

AF:

0.00589

EpiControl

AF:

0.00717

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 21, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

GCC2-related disorder

Benign:1

May 21, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

BayesDel_noAF

Benign

-0.50

CADD

Benign

7.5

DANN

Benign

0.50

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