chr7-130613558-G-C

Position:

• chr7-130613558-G-C

Variant summary

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

The NM_012133.6(COPG2):​c.478C>G​(p.Leu160Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: COPG2 NM_012133.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.00700

Genes affected

COPG2 (HGNC:2237): (COPI coat complex subunit gamma 2) Predicted to enable structural molecule activity. Involved in intra-Golgi vesicle-mediated transport. Part of COPI vesicle coat. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COPG2	NM_012133.6	c.478C>G	p.Leu160Val	missense_variant	7/24	ENST00000425248.5
COPG2	NM_001290033.2	c.478C>G	p.Leu160Val	missense_variant	7/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COPG2	ENST00000425248.5	c.478C>G	p.Leu160Val	missense_variant	7/24	1	NM_012133.6	P1
COPG2	ENST00000330992.8	c.478C>G	p.Leu160Val	missense_variant	7/20	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

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

May 05, 2023

The c.478C>G (p.L160V) alteration is located in exon 1 (coding exon 1) of the COPG2 gene. This alteration results from a C to G substitution at nucleotide position 478, causing the leucine (L) at amino acid position 160 to be replaced by a valine (V). 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	Uncertain	0.49
BayesDel_addAF	Benign	-0.0046	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;.
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.21	N
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.56	D;D
MetaSVM	Benign	-0.69	T
MutationTaster	Benign	0.97	D
PrimateAI	Uncertain	0.78	T
Sift4G	Uncertain	0.0020	D;D
Polyphen		0.99	D;.
Vest4		0.60
MutPred		0.69		Gain of catalytic residue at L160 (P = 0.0024);Gain of catalytic residue at L160 (P = 0.0024);
MVP		0.59
ClinPred		0.98	D
GERP RS		-4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.089
gMVP		0.52

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

Other links and lift over

dbSNP: rs1563059700; hg19: chr7-130298429;