rs4934719

Positions:

• chr10-35087841-T-C

Variant summary

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

The NM_003591.4(CUL2):​c.-23+2338A>G 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 151,814 control chromosomes in the GnomAD database, including 7,047 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 (7047 hom., cov: 32)
• Consequence: CUL2 NM_003591.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.580

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]

CUL2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CUL2	NM_003591.4	c.-23+2338A>G		intron_variant		ENST00000374749.8	NP_003582.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUL2	ENST00000374749.8	c.-23+2338A>G		intron_variant		1	NM_003591.4	ENSP00000363881.3

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44443 AN: 151694 Hom.: 7036 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.293 AC: 44488 AN: 151814 Hom.: 7047 Cov.: 32 AF XY: 0.296 AC XY: 21929 AN XY: 74158

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.300

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.297

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.324

Alfa AF: 0.326 Hom.: 4111

Bravo AF: 0.279

Asia WGS AF: 0.341 AC: 1185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.0
DANN	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs4934719; hg19: chr10-35376769;