15-49133803-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_004236.4(COPS2):c.903G>A(p.Pro301=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00056 in 1,597,404 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0030 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00030 (2 hom.)
• Consequence: COPS2 NM_004236.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.436

Genes affected

COPS2 (HGNC:30747): (COP9 signalosome subunit 2) Predicted to enable transcription corepressor activity. Involved in protein deneddylation and protein phosphorylation. Located in cytoplasm. Part of COP9 signalosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.2).
• BP6: Variant 15-49133803-C-T is Benign according to our data. Variant chr15-49133803-C-T is described in ClinVar as [Benign]. Clinvar id is 788586.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.436 with no splicing effect.
• BS2: High AC in GnomAd at 459 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COPS2	NM_004236.4	c.903G>A	p.Pro301=	synonymous_variant	9/13	ENST00000388901.10
COPS2	NM_001143887.2	c.924G>A	p.Pro308=	synonymous_variant	9/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COPS2	ENST00000388901.10	c.903G>A	p.Pro301=	synonymous_variant	9/13	1	NM_004236.4	P4
COPS2	ENST00000299259.10	c.924G>A	p.Pro308=	synonymous_variant	9/13	1		A1
COPS2	ENST00000542928.5	c.711G>A	p.Pro237=	synonymous_variant	7/11	2

Frequencies

GnomAD3 genomes AF: 0.00302 AC: 459 AN: 151988 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

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: 0.0000588

Gnomad OTH AF: 0.00336

GnomAD3 exomes AF: 0.000811 AC: 192 AN: 236728 Hom.: 2 AF XY: 0.000687 AC XY: 88 AN XY: 128016

Gnomad AFR exome AF: 0.0112

Gnomad AMR exome AF: 0.000192

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000115

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000550

Gnomad OTH exome AF: 0.000349

GnomAD4 exome AF: 0.000302 AC: 436 AN: 1445298 Hom.: 2 Cov.: 29 AF XY: 0.000298 AC XY: 214 AN XY: 718588

Gnomad4 AFR exome AF: 0.0114

Gnomad4 AMR exome AF: 0.000291

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000507

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.0000217

Gnomad4 OTH exome AF: 0.000435

GnomAD4 genome AF: 0.00301 AC: 458 AN: 152106 Hom.: 2 Cov.: 33 AF XY: 0.00297 AC XY: 221 AN XY: 74366

Gnomad4 AFR AF: 0.0104

Gnomad4 AMR AF: 0.000982

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.00158 Hom.: 2

Bravo AF: 0.00343

Asia WGS AF: 0.000578 AC: 2 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.20
Cadd	Benign	13
Dann	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs148364582; hg19: chr15-49426000; COSMIC: COSV54646159; COSMIC: COSV54646159;