chr15-75843742-A-G

Position:

• chr15-75843742-A-G

Variant summary

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

The NM_173469.4(UBE2Q2):​c.76A>G​(p.Ile26Val) 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: UBE2Q2 NM_173469.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.09

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]

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=0.23104462).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE2Q2	NM_173469.4	c.76A>G	p.Ile26Val	missense_variant	1/13	ENST00000267938.9	NP_775740.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE2Q2	ENST00000267938.9	c.76A>G	p.Ile26Val	missense_variant	1/13	1	NM_173469.4	ENSP00000267938.4
UBE2Q2	ENST00000569423.5	c.76A>G	p.Ile26Val	missense_variant	1/12	2		ENSP00000456324.1
UBE2Q2	ENST00000561723.5	n.76A>G		non_coding_transcript_exon_variant	1/5	4		ENSP00000458006.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Oct 13, 2023

The c.76A>G (p.I26V) alteration is located in exon 1 (coding exon 1) of the UBE2Q2 gene. This alteration results from a A to G substitution at nucleotide position 76, causing the isoleucine (I) at amino acid position 26 to be replaced by a valine (V). 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	0.17
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0059	T;.
Eigen	Benign	0.033
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Uncertain	0.085	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.0	L;L
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.22	N;N
REVEL	Benign	0.069
Sift	Benign	0.32	T;T
Sift4G	Benign	0.42	T;T
Polyphen		0.30	B;.
Vest4		0.25
MutPred		0.37		Loss of catalytic residue at I26 (P = 0.0561);Loss of catalytic residue at I26 (P = 0.0561);
MVP		0.46
MPC		0.23
ClinPred		0.75	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.30

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: chr15-76136083;