Genetic Variant CUEDC2:p.Gln163Arg (chr10-102424102-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024040.3(CUEDC2):c.488A>G(p.Gln163Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CUEDC2
NM_024040.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.30

Variant links:

Genes affected

CUEDC2 (HGNC:28352): (CUE domain containing 2) Predicted to enable ubiquitin binding activity. Acts upstream of or within negative regulation of cytokine production involved in inflammatory response and negative regulation of macrophage cytokine production. Located in cytosol; nuclear membrane; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CUEDC2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16076884).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUEDC2	NM_024040.3 link	c.488A>G	p.Gln163Arg	missense_variant	Exon 6 of 9	ENST00000369937.5	NP_076945.2	Q9H467

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CUEDC2	ENST00000369937.5 link	c.488A>G	p.Gln163Arg	missense_variant	Exon 6 of 9	1	NM_024040.3	ENSP00000358953.4	Q9H467
CUEDC2	ENST00000465409.1 link	n.203A>G		non_coding_transcript_exon_variant	Exon 1 of 3	2
CUEDC2	ENST00000477994.1 link	n.642A>G		non_coding_transcript_exon_variant	Exon 5 of 5	2
CUEDC2	ENST00000486762.6 link	n.457A>G		non_coding_transcript_exon_variant	Exon 5 of 5	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461846

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727230

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:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

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

Aug 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.488A>G (p.Q163R) alteration is located in exon 6 (coding exon 5) of the CUEDC2 gene. This alteration results from a A to G substitution at nucleotide position 488, causing the glutamine (Q) at amino acid position 163 to be replaced by an arginine (R). 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

0.10

BayesDel_addAF

Benign

0.0089

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.037

Eigen

Benign

-0.12

Eigen_PC

Benign

0.058

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.58

M_CAP

Benign

0.081

MetaRNN

Benign

0.16

MetaSVM

Uncertain

-0.14

MutationAssessor

Benign

0.34

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.7

REVEL

Uncertain

0.31

Sift

Benign

0.056

Sift4G

Benign

0.13

Polyphen

0.035

Vest4

0.31

MutPred

0.44

Gain of MoRF binding (P = 0.0241);

MVP

0.88

MPC

1.0

ClinPred

0.64

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.63

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