NM_003591.4:c.913T>A

Variant names:

• chr10-35035261-A-T
• NM_003591.4:c.913T>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003591.4(CUL2):​c.913T>A​(p.Ser305Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CUL2 NM_003591.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.47
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003591.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUL2	NM_003591.4	MANE Select	c.913T>A	p.Ser305Thr	missense	Exon 10 of 21	NP_003582.2
	CUL2	NM_001198778.2		c.970T>A	p.Ser324Thr	missense	Exon 10 of 21	NP_001185707.1	Q13617-2
	CUL2	NM_001198779.1		c.952T>A	p.Ser318Thr	missense	Exon 10 of 21	NP_001185708.1	Q13617

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUL2	ENST00000374749.8	TSL:1 MANE Select	c.913T>A	p.Ser305Thr	missense	Exon 10 of 21	ENSP00000363881.3	Q13617-1
	CUL2	ENST00000374751.7	TSL:1	c.913T>A	p.Ser305Thr	missense	Exon 10 of 21	ENSP00000363883.3	Q13617-1
	CUL2	ENST00000970364.1		c.979T>A	p.Ser327Thr	missense	Exon 11 of 22	ENSP00000640423.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Benign	0.89
DEOGEN2	Uncertain	0.42	T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.13
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.46	N
PhyloP100		4.5
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.080
Sift	Benign	0.22	T
Sift4G	Benign	0.51	T
Polyphen		0.0030	B
Vest4		0.43
MutPred		0.37		Loss of MoRF binding (P = 0.1947)
MVP		0.44
MPC		0.79
ClinPred		0.82	D
GERP RS		6.0
Varity_R		0.22
gMVP		0.12
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.22		Position offset: -27

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

Other links and lift over

hg19: chr10-35324189;