rs2072575

Positions:

• chr7-130508666-G-A
• chr7-130508666-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012133.6(COPG2):​c.2150-7C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 753,252 control chromosomes in the GnomAD database, including 101,888 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.43 (16664 hom., cov: 31)
  • Exomes 𝑓: 0.53 (85224 hom.)
• Consequence: COPG2 NM_012133.6 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.293

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COPG2	NM_012133.6	c.2150-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000425248.5	NP_036265.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COPG2	ENST00000425248.5	c.2150-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_012133.6	ENSP00000402346	P1
COPG2	ENST00000617523.1	n.1531-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64594 AN: 151876 Hom.: 16664 Cov.: 31

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.443

GnomAD3 exomes AF: 0.515 AC: 105474 AN: 204932 Hom.: 27868 AF XY: 0.516 AC XY: 56747 AN XY: 109946

Gnomad AFR exome AF: 0.107

Gnomad AMR exome AF: 0.537

Gnomad ASJ exome AF: 0.519

Gnomad EAS exome AF: 0.590

Gnomad SAS exome AF: 0.491

Gnomad FIN exome AF: 0.564

Gnomad NFE exome AF: 0.546

Gnomad OTH exome AF: 0.504

GnomAD4 exome AF: 0.526 AC: 316096 AN: 601258 Hom.: 85224 Cov.: 0 AF XY: 0.524 AC XY: 170805 AN XY: 325808

Gnomad4 AFR exome AF: 0.115

Gnomad4 AMR exome AF: 0.527

Gnomad4 ASJ exome AF: 0.512

Gnomad4 EAS exome AF: 0.602

Gnomad4 SAS exome AF: 0.482

Gnomad4 FIN exome AF: 0.562

Gnomad4 NFE exome AF: 0.547

Gnomad4 OTH exome AF: 0.498

GnomAD4 genome AF: 0.425 AC: 64601 AN: 151994 Hom.: 16664 Cov.: 31 AF XY: 0.429 AC XY: 31887 AN XY: 74272

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.515

Gnomad4 ASJ AF: 0.534

Gnomad4 EAS AF: 0.586

Gnomad4 SAS AF: 0.493

Gnomad4 FIN AF: 0.564

Gnomad4 NFE AF: 0.548

Gnomad4 OTH AF: 0.441

Alfa AF: 0.479 Hom.: 8217

Bravo AF: 0.410

Asia WGS AF: 0.530 AC: 1842 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.5
DANN	Benign	0.80

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2072575; hg19: chr7-130148507; COSMIC: COSV56227574; COSMIC: COSV56227574;