2-108469005-T-C

Position:

• chr2-108469005-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_181453.4(GCC2):​c.242T>C​(p.Leu81Pro) 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: 6.10

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24118918).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GCC2	NM_181453.4	c.242T>C	p.Leu81Pro	missense_variant	5/23	ENST00000309863.11	NP_852118.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GCC2	ENST00000309863.11	c.242T>C	p.Leu81Pro	missense_variant	5/23	5	NM_181453.4	ENSP00000307939.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 30, 2021

The c.242T>C (p.L81P) alteration is located in exon 5 (coding exon 5) of the GCC2 gene. This alteration results from a T to C substitution at nucleotide position 242, causing the leucine (L) at amino acid position 81 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.059	T;T;T
Eigen	Benign	0.062
Eigen_PC	Benign	0.17
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.50	T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N;.;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.6	N;D;N
REVEL	Benign	0.19
Sift	Uncertain	0.0010	D;D;D
Sift4G	Benign	0.14	T;T;D
Polyphen		0.57	P;.;.
Vest4		0.47
MutPred		0.33		Loss of stability (P = 2e-04);.;.;
MVP		0.43
MPC		0.12
ClinPred		0.93	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.50
gMVP		0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-109085461;