chr10-102424328-C-T

Variant names:

• chr10-102424328-C-T
• rs550946332
• NM_024040.3:c.347G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_024040.3(CUEDC2):​c.347G>A​(p.Arg116Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000892 in 1,614,138 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict 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. R116W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000093 (3 hom.)
• Consequence: CUEDC2 NM_024040.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.649
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008251399).
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024040.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUEDC2	NM_024040.3	MANE Select	c.347G>A	p.Arg116Gln	missense	Exon 5 of 9	NP_076945.2	Q9H467

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUEDC2	ENST00000369937.5	TSL:1 MANE Select	c.347G>A	p.Arg116Gln	missense	Exon 5 of 9	ENSP00000358953.4	Q9H467
	CUEDC2	ENST00000888785.1		c.347G>A	p.Arg116Gln	missense	Exon 5 of 9	ENSP00000558844.1
	CUEDC2	ENST00000925790.1		c.347G>A	p.Arg116Gln	missense	Exon 5 of 9	ENSP00000595849.1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152170 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000192 AC: 48 AN: 249516 AF XY: 0.000229

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.0000883

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.0000930 AC: 136 AN: 1461850 Hom.: 3 Cov.: 35 AF XY: 0.000122 AC XY: 89 AN XY: 727232

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.00109 AC: 94 AN: 86248

European-Finnish (FIN) AF: 0.000131 AC: 7 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000243 AC: 27 AN: 1112002

Other (OTH) AF: 0.0000828 AC: 5 AN: 60392

GnomAD4 genome AF: 0.0000525 AC: 8 AN: 152288 Hom.: 0 Cov.: 33 AF XY: 0.0000671 AC XY: 5 AN XY: 74468

African (AFR) AF: 0.00 AC: 0 AN: 41528

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4830

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000823 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.000182 AC: 22

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	4.3
DANN	Benign	0.91
DEOGEN2	Benign	0.021	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.095	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.0083	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	-0.51	N
PhyloP100		-0.65
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.25	N
REVEL	Benign	0.25
Sift	Benign	0.49	T
Sift4G	Benign	0.57	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.17		Loss of helix (P = 0.0304)
MVP		0.77
MPC		0.48
ClinPred		0.016	T
GERP RS		1.4
Varity_R		0.017
gMVP		0.26
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs550946332; hg19: chr10-104184085; COSMIC: COSV99827956; COSMIC: COSV99827956;