chr10-35100915-T-C

Variant names:

• chr10-35100915-T-C
• rs12768019
• ENST00000685421.1:c.96A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000685421.1(CUL2):​c.96A>G​(p.Lys32Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 151,980 control chromosomes in the GnomAD database, including 7,043 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 (7040 hom., cov: 31)
  • Exomes 𝑓: 0.40 (3 hom.)
• Consequence: CUL2 ENST00000685421.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01
• 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]

ENSG00000230534 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP7: Synonymous conserved (PhyloP=-2.01 with no splicing effect.
• 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 rank	MANE	Protein	UniProt
CUL2	XM_011519743.1	c.96A>G	p.Lys32Lys	synonymous_variant	Exon 3 of 23		XP_011518045.1
CUL2	XM_011519744.1	c.96A>G	p.Lys32Lys	synonymous_variant	Exon 2 of 22		XP_011518046.1
CUL2	XM_011519745.2	c.96A>G	p.Lys32Lys	synonymous_variant	Exon 2 of 22		XP_011518047.1
CUL2	XM_047425852.1	c.96A>G	p.Lys32Lys	synonymous_variant	Exon 3 of 23		XP_047281808.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUL2	ENST00000685421.1	c.96A>G	p.Lys32Lys	synonymous_variant	Exon 2 of 6			ENSP00000509605.1
CUL2	ENST00000686156.1	c.96A>G	p.Lys32Lys	synonymous_variant	Exon 2 of 6			ENSP00000509166.1
CUL2	ENST00000688736.1	c.96A>G	p.Lys32Lys	synonymous_variant	Exon 3 of 7			ENSP00000510643.1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44416 AN: 151794 Hom.: 7028 Cov.: 31

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.316

GnomAD4 exome AF: 0.397 AC: 27 AN: 68 Hom.: 3 Cov.: 0 AF XY: 0.413 AC XY: 19 AN XY: 46

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.414 AC: 24 AN: 58

Other (OTH) AF: 0.333 AC: 2 AN: 6

GnomAD4 genome AF: 0.293 AC: 44464 AN: 151912 Hom.: 7040 Cov.: 31 AF XY: 0.295 AC XY: 21913 AN XY: 74218

African (AFR) AF: 0.163 AC: 6750 AN: 41490

American (AMR) AF: 0.298 AC: 4534 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1385 AN: 3470

East Asian (EAS) AF: 0.294 AC: 1514 AN: 5156

South Asian (SAS) AF: 0.347 AC: 1667 AN: 4806

European-Finnish (FIN) AF: 0.391 AC: 4113 AN: 10530

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

European-Non Finnish (NFE) AF: 0.346 AC: 23497 AN: 67938

Other (OTH) AF: 0.323 AC: 681 AN: 2110

Alfa AF: 0.325 Hom.: 4554

Bravo AF: 0.279

Asia WGS AF: 0.342 AC: 1188 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.38
DANN	Benign	0.27
PhyloP100		-2.0

Splicing

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

Other links and lift over

dbSNP: rs12768019; hg19: chr10-35389843;