NM_181453.4:c.227A>G

Variant names:

• chr2-108468990-A-G
• NM_181453.4:c.227A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_181453.4(GCC2):​c.227A>G​(p.Glu76Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GCC2 NM_181453.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.39
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21639773).

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.227A>G	p.Glu76Gly	missense	Exon 5 of 23	NP_852118.2	Q8IWJ2-1
	GCC2	NM_001410194.1		c.-77A>G		5_prime_UTR	Exon 4 of 22	NP_001397123.1	A0A8I5QJB7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCC2	ENST00000309863.11	TSL:5 MANE Select	c.227A>G	p.Glu76Gly	missense	Exon 5 of 23	ENSP00000307939.5	Q8IWJ2-1
	GCC2	ENST00000482325.5	TSL:1	n.*4A>G		non_coding_transcript_exon	Exon 4 of 22	ENSP00000419969.1	Q8IWJ2-3
	GCC2	ENST00000482325.5	TSL:1	n.*4A>G		3_prime_UTR	Exon 4 of 22	ENSP00000419969.1	Q8IWJ2-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.4
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.12
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.019	D
Polyphen		0.96	D
Vest4		0.36
MutPred		0.17		Gain of methylation at R77 (P = 0.048)
MVP		0.52
MPC		0.083
ClinPred		0.87	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.33
gMVP		0.25
Mutation Taster		=58/42	polymorphism

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

Other links and lift over

hg19: chr2-109085446;