rs1926554

Variant names:

• chr10-35056041-C-T
• rs1926554
• NM_003591.4:c.318-1502G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003591.4(CUL2):​c.318-1502G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,052 control chromosomes in the GnomAD database, including 7,443 homozygotes. 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: 𝑓 0.31 (7443 hom., cov: 32)
• Consequence: CUL2 NM_003591.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 20 publications found

Genes affected

CUL2 (HGNC:2552): (cullin 2) Enables ubiquitin protein ligase binding activity. Predicted to be involved in SCF-dependent proteasomal ubiquitin-dependent protein catabolic process and protein ubiquitination. Predicted to act upstream of or within protein catabolic process. Located in nucleoplasm. Part of Cul2-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003591.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUL2	NM_003591.4	MANE Select	c.318-1502G>A		intron	N/A	NP_003582.2
	CUL2	NM_001198778.2		c.375-1502G>A		intron	N/A	NP_001185707.1
	CUL2	NM_001198779.1		c.357-1502G>A		intron	N/A	NP_001185708.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUL2	ENST00000374749.8	TSL:1 MANE Select	c.318-1502G>A		intron	N/A	ENSP00000363881.3
	CUL2	ENST00000374751.7	TSL:1	c.318-1502G>A		intron	N/A	ENSP00000363883.3
	CUL2	ENST00000421317.5	TSL:2	c.375-1502G>A		intron	N/A	ENSP00000414095.2

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46547 AN: 151934 Hom.: 7426 Cov.: 32

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.327

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.307 AC: 46617 AN: 152052 Hom.: 7443 Cov.: 32 AF XY: 0.309 AC XY: 22930 AN XY: 74324

African (AFR) AF: 0.210 AC: 8726 AN: 41480

American (AMR) AF: 0.305 AC: 4652 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1352 AN: 3470

East Asian (EAS) AF: 0.295 AC: 1523 AN: 5168

South Asian (SAS) AF: 0.348 AC: 1678 AN: 4826

European-Finnish (FIN) AF: 0.391 AC: 4126 AN: 10546

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23532 AN: 67980

Other (OTH) AF: 0.333 AC: 704 AN: 2112

Alfa AF: 0.334 Hom.: 26887

Bravo AF: 0.295

Asia WGS AF: 0.348 AC: 1209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.17
DANN	Benign	0.64
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs1926554; hg19: chr10-35344969;