6-42603687-G-C

Variant names:

• chr6-42603687-G-C
• NM_001363705.2:c.631G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001363705.2(UBR2):​c.631G>C​(p.Glu211Gln) variant causes a missense change involving the alteration of a conserved nucleotide. 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: UBR2 NM_001363705.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.33

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18472934).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBR2	NM_001363705.2	c.631G>C	p.Glu211Gln	missense_variant	Exon 5 of 47	ENST00000372901.2	NP_001350634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBR2	ENST00000372901.2	c.631G>C	p.Glu211Gln	missense_variant	Exon 5 of 47	5	NM_001363705.2	ENSP00000361992.1
UBR2	ENST00000372899.6	c.631G>C	p.Glu211Gln	missense_variant	Exon 5 of 47	1		ENSP00000361990.1
UBR2	ENST00000372903.6	c.631G>C	p.Glu211Gln	missense_variant	Exon 5 of 12	1		ENSP00000361994.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.631G>C (p.E211Q) alteration is located in exon 5 (coding exon 5) of the UBR2 gene. This alteration results from a G to C substitution at nucleotide position 631, causing the glutamic acid (E) at amino acid position 211 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	.;T;.
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	2.0	M;M;M
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.73	N;N;N
REVEL	Benign	0.15
Sift	Benign	0.18	T;T;T
Sift4G	Benign	0.37	T;T;T
Polyphen		0.13	B;B;.
Vest4		0.29
MutPred		0.29		Loss of disorder (P = 0.0753);Loss of disorder (P = 0.0753);Loss of disorder (P = 0.0753);
MVP		0.47
MPC		0.47
ClinPred		0.71	D
GERP RS		5.6
Varity_R		0.084
gMVP		0.51

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-42571425;