Variant 15-49128083-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The ENST00000388901.10(COPS2):c.1199G>T(p.Gly400Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,150 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

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: 7.68

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.936

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COPS2	NM_004236.4 linkuse as main transcript	c.1199G>T	p.Gly400Val	missense_variant	13/13	ENST00000388901.10	NP_004227.1
COPS2	NM_001143887.2 linkuse as main transcript	c.1220G>T	p.Gly407Val	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.1199G>T	p.Gly400Val	missense_variant	13/13	1	NM_004236.4	ENSP00000373553	P4	P61201-1
COPS2	ENST00000299259.10 linkuse as main transcript	c.1220G>T	p.Gly407Val	missense_variant	13/13	1		ENSP00000299259	A1	P61201-2
COPS2	ENST00000542928.5 linkuse as main transcript	c.1007G>T	p.Gly336Val	missense_variant	11/11	2		ENSP00000443664
COPS2	ENST00000560240.5 linkuse as main transcript	c.138+1394G>T		intron_variant, NMD_transcript_variant		4		ENSP00000453546

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461150

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726836

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:

9.00e-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

May 14, 2024

The c.1220G>T (p.G407V) alteration is located in exon 13 (coding exon 13) of the COPS2 gene. This alteration results from a G to T substitution at nucleotide position 1220, causing the glycine (G) at amino acid position 407 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

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.34

BayesDel_noAF

Pathogenic

0.25

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

T;.;T

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.95

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

0.99

D;D;D

M_CAP

Benign

0.078

MetaRNN

Pathogenic

0.94

D;D;D

MetaSVM

Uncertain

0.24

MutationAssessor

Pathogenic

3.5

H;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.94

PROVEAN

Pathogenic

-6.6

D;D;D

REVEL

Pathogenic

0.70

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.95

MutPred

0.80

Loss of catalytic residue at G400 (P = 0.0385);.;.;

MVP

0.76

MPC

1.4

ClinPred

0.99

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.96

gMVP

0.96

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