rs11592567

Positions:

• chr10-35120441-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000688736.1(CUL2):​c.-81G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 151,976 control chromosomes in the GnomAD database, including 7,057 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 0.29 (7057 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: CUL2 ENST00000688736.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

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]

ENSG00000230534 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CUL2	XM_011519743.1	c.-81G>A		5_prime_UTR_variant	2/23		XP_011518045.1
CUL2	XM_047425852.1	c.-81G>A		5_prime_UTR_variant	2/23		XP_047281808.1
CUL2	XM_011519744.1	c.-51+6164G>A		intron_variant			XP_011518046.1
CUL2	XM_011519745.2	c.-51+6375G>A		intron_variant			XP_011518047.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUL2	ENST00000688736.1	c.-81G>A		5_prime_UTR_variant	2/7			ENSP00000510643.1
CUL2	ENST00000685421.1	c.-51+6164G>A		intron_variant				ENSP00000509605.1
CUL2	ENST00000686156.1	c.-51+6375G>A		intron_variant				ENSP00000509166.1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44479 AN: 151856 Hom.: 7045 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.316

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.293 AC: 44524 AN: 151974 Hom.: 7057 Cov.: 32 AF XY: 0.295 AC XY: 21949 AN XY: 74290

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.296

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.323

Alfa AF: 0.309 Hom.: 962

Bravo AF: 0.279

Asia WGS AF: 0.344 AC: 1195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11592567; hg19: chr10-35409369;