10-35092445-G-A

Variant names:

• chr10-35092445-G-A
• rs11593858
• ENST00000685421.1:c.167+8399C>T

Variant summary

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

The ENST00000685421.1(CUL2):​c.167+8399C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,076 control chromosomes in the GnomAD database, including 7,063 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 (7063 hom., cov: 33)
• Consequence: CUL2 ENST00000685421.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.230
• Publications: 12 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=-0.72).
• 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: ENST00000685421.1. 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUL2	ENST00000685421.1		c.167+8399C>T		intron	N/A	ENSP00000509605.1
	CUL2	ENST00000686156.1		c.167+8399C>T		intron	N/A	ENSP00000509166.1
	CUL2	ENST00000688736.1		c.167+8399C>T		intron	N/A	ENSP00000510643.1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44523 AN: 151958 Hom.: 7051 Cov.: 33

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.293 AC: 44571 AN: 152076 Hom.: 7063 Cov.: 33 AF XY: 0.296 AC XY: 21974 AN XY: 74330

African (AFR) AF: 0.163 AC: 6778 AN: 41504

American (AMR) AF: 0.299 AC: 4562 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1387 AN: 3470

East Asian (EAS) AF: 0.295 AC: 1525 AN: 5176

South Asian (SAS) AF: 0.347 AC: 1674 AN: 4822

European-Finnish (FIN) AF: 0.391 AC: 4117 AN: 10542

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23520 AN: 67968

Other (OTH) AF: 0.324 AC: 684 AN: 2110

Alfa AF: 0.325 Hom.: 4576

Bravo AF: 0.279

Asia WGS AF: 0.340 AC: 1182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	3.0
DANN	Benign	0.75
PhyloP100		-0.23

Splicing

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

Other links and lift over

dbSNP: rs11593858; hg19: chr10-35381373;