8-48049916-C-T

Variant names:

• chr8-48049916-C-T
• rs2091524316
• NM_003350.3:c.229C>T

Variant summary

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

The NM_003350.3(UBE2V2):​c.229C>T​(p.Pro77Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UBE2V2 NM_003350.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.73

Genes affected

UBE2V2 (HGNC:12495): (ubiquitin conjugating enzyme E2 V2) Ubiquitin-conjugating enzyme E2 variant proteins constitute a distinct subfamily within the E2 protein family. They have sequence similarity to other ubiquitin-conjugating enzymes but lack the conserved cysteine residue that is critical for the catalytic activity of E2s. The protein encoded by this gene also shares homology with ubiquitin-conjugating enzyme E2 variant 1 and yeast MMS2 gene product. It may be involved in the differentiation of monocytes and enterocytes. [provided by RefSeq, Jul 2008]

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 rank	MANE	Protein	UniProt
UBE2V2	NM_003350.3	c.229C>T	p.Pro77Ser	missense_variant	Exon 3 of 4	ENST00000523111.7	NP_003341.1
UBE2V2	XM_011517583.4	c.313C>T	p.Pro105Ser	missense_variant	Exon 3 of 4		XP_011515885.1
UBE2V2	XM_017013808.3	c.310C>T	p.Pro104Ser	missense_variant	Exon 3 of 4		XP_016869297.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE2V2	ENST00000523111.7	c.229C>T	p.Pro77Ser	missense_variant	Exon 3 of 4	1	NM_003350.3	ENSP00000428209.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 06, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.229C>T (p.P77S) alteration is located in exon 3 (coding exon 3) of the UBE2V2 gene. This alteration results from a C to T substitution at nucleotide position 229, causing the proline (P) at amino acid position 77 to be replaced by a serine (S). 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	Uncertain	0.41
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T;T;T;T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.87	D;.;.;D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.50	D;D;D;D
MetaSVM	Benign	-0.42	T
MutationAssessor	Pathogenic	3.0	M;.;.;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-6.0	D;D;D;D
REVEL	Uncertain	0.29
Sift	Uncertain	0.014	D;D;D;D
Sift4G	Uncertain	0.016	D;D;D;D
Polyphen		0.86	P;.;.;.
Vest4		0.41
MutPred		0.77		Loss of catalytic residue at P77 (P = 0.0291);.;.;.;
MVP		0.83
MPC		0.84
ClinPred		0.99	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.74
gMVP		0.61

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

LitVar

Other links and lift over

dbSNP: rs2091524316; hg19: chr8-48962476; COSMIC: COSV72878757;