10-102424140-A-G

Variant names:

• chr10-102424140-A-G
• rs373178334
• NM_024040.3:c.450T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024040.3(CUEDC2):​c.450T>C​(p.Asp150Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CUEDC2 NM_024040.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).

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.450T>C	p.Asp150Asp	synonymous	Exon 6 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.450T>C	p.Asp150Asp	synonymous	Exon 6 of 9	ENSP00000358953.4	Q9H467
	CUEDC2	ENST00000888785.1		c.456T>C	p.Asp152Asp	synonymous	Exon 6 of 9	ENSP00000558844.1
	CUEDC2	ENST00000925790.1		c.456T>C	p.Asp152Asp	synonymous	Exon 6 of 9	ENSP00000595849.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461800 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 727220

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: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111976

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.8
DANN	Benign	0.55
PhyloP100		-0.069

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

Other links and lift over

dbSNP: rs373178334; hg19: chr10-104183897;