Genetic Variant GCC2:p.Gln258His (chr2-108470103-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_181453.4(GCC2):c.774G>T(p.Gln258His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000793 in 1,613,396 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000084 ( 0 hom. )

Consequence

GCC2
NM_181453.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.901

Publications

1 publications found

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-AS1 (HGNC:28126): (GCC2 antisense RNA 1)

GCC2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.056085855).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181453.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCC2	NM_181453.4	MANE Select	c.774G>T	p.Gln258His	missense	Exon 6 of 23	NP_852118.2	Q8IWJ2-1
	GCC2	NM_001410194.1		c.471G>T	p.Gln157His	missense	Exon 5 of 22	NP_001397123.1	A0A8I5QJB7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GCC2	ENST00000309863.11	TSL:5 MANE Select	c.774G>T	p.Gln258His	missense	Exon 6 of 23	ENSP00000307939.5	Q8IWJ2-1
GCC2	ENST00000482325.5	TSL:1	n.*551G>T		non_coding_transcript_exon	Exon 5 of 22	ENSP00000419969.1	Q8IWJ2-3
GCC2	ENST00000482325.5	TSL:1	n.*551G>T		3_prime_UTR	Exon 5 of 22	ENSP00000419969.1	Q8IWJ2-3

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152182

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000722

AC:

AN:

249380

AF XY:

0.0000666

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:

0.0000462

Gnomad NFE exome

AF:

0.000134

Gnomad OTH exome

AF:

0.000329

GnomAD4 exome

AF:

0.0000842

AC:

123

AN:

1461214

Hom.:

Cov.:

AF XY:

0.0000784

AC XY:

AN XY:

726946

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33462

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39656

South Asian (SAS)

AF:

0.00

AC:

AN:

86236

European-Finnish (FIN)

AF:

0.0000938

AC:

AN:

53324

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000104

AC:

116

AN:

1111558

Other (OTH)

AF:

0.0000331

AC:

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

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

AF:

0.0000329

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41448

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000582

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000906

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.54

CADD

Benign

4.5

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.091

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.079

LIST_S2

Benign

0.75

M_CAP

Benign

0.0057

MetaRNN

Benign

0.056

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

PhyloP100

-0.90

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.6

REVEL

Benign

0.065

Sift

Benign

0.10

Sift4G

Benign

0.072

Polyphen

0.016

Vest4

0.19

MutPred

0.093

Loss of methylation at K253 (P = 0.1226)

MVP

0.13

MPC

0.054

ClinPred

0.068

GERP RS

-7.7

Varity_R

0.053

gMVP

0.32

Mutation Taster

=91/9

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over