15-75843701-T-A

Position:

• chr15-75843701-T-A

Variant summary

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

The NM_173469.4(UBE2Q2):​c.35T>A​(p.Phe12Tyr) 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: 4.10

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=0.15246093).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE2Q2	NM_173469.4	c.35T>A	p.Phe12Tyr	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.35T>A	p.Phe12Tyr	missense_variant	1/13	1	NM_173469.4	ENSP00000267938.4
UBE2Q2	ENST00000569423.5	c.35T>A	p.Phe12Tyr	missense_variant	1/12	2		ENSP00000456324.1
UBE2Q2	ENST00000561723.5	n.35T>A		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

Apr 29, 2024

The c.35T>A (p.F12Y) alteration is located in exon 1 (coding exon 1) of the UBE2Q2 gene. This alteration results from a T to A substitution at nucleotide position 35, causing the phenylalanine (F) at amino acid position 12 to be replaced by a tyrosine (Y). 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	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Benign	0.94
DEOGEN2	Benign	0.010	T;.
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.026
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.81	T;D
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.41	N;N
REVEL	Benign	0.055
Sift	Benign	0.14	T;T
Sift4G	Benign	0.65	T;T
Polyphen		0.062	B;.
Vest4		0.34
MutPred		0.36		Loss of methylation at K11 (P = 0.0331);Loss of methylation at K11 (P = 0.0331);
MVP		0.40
MPC		0.78
ClinPred		0.55	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.34

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: chr15-76136042;