15-75859908-G-A

Position:

• chr15-75859908-G-A

Variant summary

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

The NM_173469.4(UBE2Q2):​c.313G>A​(p.Glu105Lys) 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: UBE2Q2 NM_173469.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.68

Genes affected

UBE2Q2 (HGNC:19248): (ubiquitin conjugating enzyme E2 Q2) Enables ubiquitin-protein transferase activity. Involved in protein K48-linked ubiquitination. Predicted to be located in cytosol. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

UBE2Q2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE2Q2	NM_173469.4	c.313G>A	p.Glu105Lys	missense_variant	3/13	ENST00000267938.9	NP_775740.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE2Q2	ENST00000267938.9	c.313G>A	p.Glu105Lys	missense_variant	3/13	1	NM_173469.4	ENSP00000267938.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 20, 2023

The c.313G>A (p.E105K) alteration is located in exon 3 (coding exon 3) of the UBE2Q2 gene. This alteration results from a G to A substitution at nucleotide position 313, causing the glutamic acid (E) at amino acid position 105 to be replaced by a lysine (K). 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	0.31
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;.
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.32	T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.17
Sift	Uncertain	0.017	D;D
Sift4G	Benign	0.16	T;T
Polyphen		0.15	B;.
Vest4		0.50
MutPred		0.50		Gain of MoRF binding (P = 0.0037);.;
MVP		0.62
MPC		0.25
ClinPred		0.98	D
GERP RS		5.2
Varity_R		0.39
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.34		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.34		Position offset: -30

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

Publications

LitVar

Other links and lift over

dbSNP: rs1897123411; hg19: chr15-76152249;