rs11010082

Variant names:

• chr10-35062227-A-G
• rs11010082
• NM_003591.4:c.222+733T>C

Variant summary

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

The NM_003591.4(CUL2):​c.222+733T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 151,970 control chromosomes in the GnomAD database, including 10,493 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 0.37 (10493 hom., cov: 31)
• Consequence: CUL2 NM_003591.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUL2	NM_003591.4	c.222+733T>C		intron_variant	Intron 3 of 20	ENST00000374749.8	NP_003582.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUL2	ENST00000374749.8	c.222+733T>C		intron_variant	Intron 3 of 20	1	NM_003591.4	ENSP00000363881.3

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56032 AN: 151852 Hom.: 10464 Cov.: 31

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.369 AC: 56124 AN: 151970 Hom.: 10493 Cov.: 31 AF XY: 0.369 AC XY: 27395 AN XY: 74248

African (AFR) AF: 0.426 AC: 17662 AN: 41448

American (AMR) AF: 0.325 AC: 4950 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1353 AN: 3468

East Asian (EAS) AF: 0.317 AC: 1642 AN: 5172

South Asian (SAS) AF: 0.350 AC: 1684 AN: 4818

European-Finnish (FIN) AF: 0.390 AC: 4111 AN: 10540

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.347 AC: 23608 AN: 67970

Other (OTH) AF: 0.373 AC: 783 AN: 2098

Alfa AF: 0.358 Hom.: 1308

Bravo AF: 0.366

Asia WGS AF: 0.369 AC: 1282 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.28
DANN	Benign	0.41
PhyloP100		-1.5
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: rs11010082; hg19: chr10-35351155;