Variant 15-49128026-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000388901.10(COPS2):c.1256C>G(p.Ala419Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A419T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

COPS2
ENST00000388901.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.94

Variant links:

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]

COPS2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28605998).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COPS2	NM_004236.4 linkuse as main transcript	c.1256C>G	p.Ala419Gly	missense_variant	13/13	ENST00000388901.10	NP_004227.1
COPS2	NM_001143887.2 linkuse as main transcript	c.1277C>G	p.Ala426Gly	missense_variant	13/13		NP_001137359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COPS2	ENST00000388901.10 linkuse as main transcript	c.1256C>G	p.Ala419Gly	missense_variant	13/13	1	NM_004236.4	ENSP00000373553	P4	P61201-1
COPS2	ENST00000299259.10 linkuse as main transcript	c.1277C>G	p.Ala426Gly	missense_variant	13/13	1		ENSP00000299259	A1	P61201-2
COPS2	ENST00000542928.5 linkuse as main transcript	c.1064C>G	p.Ala355Gly	missense_variant	11/11	2		ENSP00000443664
COPS2	ENST00000560240.5 linkuse as main transcript	c.138+1451C>G		intron_variant, NMD_transcript_variant		4		ENSP00000453546

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461608

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727108

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 28, 2023

The c.1277C>G (p.A426G) alteration is located in exon 13 (coding exon 13) of the COPS2 gene. This alteration results from a C to G substitution at nucleotide position 1277, causing the alanine (A) at amino acid position 426 to be replaced by a glycine (G). 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

Benign

0.11

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.20

T;.;T

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.95

D;D;D

M_CAP

Benign

0.0078

MetaRNN

Benign

0.29

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.7

L;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.7

N;N;N

REVEL

Benign

0.25

Sift

Benign

0.31

T;T;T

Sift4G

Benign

0.32

T;T;T

Polyphen

0.0010

B;.;B

Vest4

0.49

MutPred

0.27

Gain of methylation at R420 (P = 0.0588);.;.;

MVP

0.51

MPC

0.53

ClinPred

0.85

GERP RS

5.9

Varity_R

0.49

gMVP

0.45

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over