6-42573754-C-A

Variant names:

• chr6-42573754-C-A
• rs1791315260
• NM_001363705.2:c.99C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001363705.2(UBR2):​c.99C>A​(p.Asp33Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,400,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: UBR2 NM_001363705.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.81
• Publications: 0 publications found

Genes affected

UBR2 (HGNC:21289): (ubiquitin protein ligase E3 component n-recognin 2) Enables leucine binding activity. Involved in cellular response to leucine and negative regulation of TOR signaling. Predicted to be located in cytosol. Predicted to be part of ubiquitin ligase complex. Predicted to be active in cytoplasm. Predicted to colocalize with chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14158162).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363705.2. 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
	UBR2	NM_001363705.2	MANE Select	c.99C>A	p.Asp33Glu	missense	Exon 2 of 47	NP_001350634.1	Q8IWV8-4
	UBR2	NM_015255.3		c.99C>A	p.Asp33Glu	missense	Exon 2 of 47	NP_056070.1	Q8IWV8-1
	UBR2	NM_001184801.2		c.99C>A	p.Asp33Glu	missense	Exon 2 of 12	NP_001171730.1	Q8IWV8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBR2	ENST00000372901.2	TSL:5 MANE Select	c.99C>A	p.Asp33Glu	missense	Exon 2 of 47	ENSP00000361992.1	Q8IWV8-4
	UBR2	ENST00000372899.6	TSL:1	c.99C>A	p.Asp33Glu	missense	Exon 2 of 47	ENSP00000361990.1	Q8IWV8-1
	UBR2	ENST00000372903.6	TSL:1	c.99C>A	p.Asp33Glu	missense	Exon 2 of 12	ENSP00000361994.2	Q8IWV8-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1400606 Hom.: 0 Cov.: 30 AF XY: 0.00000434 AC XY: 3 AN XY: 691314

African (AFR) AF: 0.00 AC: 0 AN: 31060

American (AMR) AF: 0.00 AC: 0 AN: 36276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24476

East Asian (EAS) AF: 0.00 AC: 0 AN: 37300

South Asian (SAS) AF: 0.00 AC: 0 AN: 78248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52446

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5564

European-Non Finnish (NFE) AF: 0.00000278 AC: 3 AN: 1077692

Other (OTH) AF: 0.00 AC: 0 AN: 57544

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	0.24
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.029
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.8
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.061
Sift	Benign	0.090	T
Sift4G	Benign	0.083	T
Polyphen		0.0080	B
Vest4		0.20
MutPred		0.53		Gain of helix (P = 0.0496)
MVP		0.34
MPC		0.39
ClinPred		0.66	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.33
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1791315260; hg19: chr6-42541492;