rs2091524316

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr8-48049916-C-A
• chr8-48049916-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_003350.3(UBE2V2):​c.229C>A​(p.Pro77Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000698 in 1,432,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: UBE2V2 NM_003350.3 missense
• Clinical Significance: Not reported in ClinVar
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.744

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE2V2	NM_003350.3	c.229C>A	p.Pro77Thr	missense_variant	Exon 3 of 4	ENST00000523111.7	NP_003341.1
UBE2V2	XM_011517583.4	c.313C>A	p.Pro105Thr	missense_variant	Exon 3 of 4		XP_011515885.1
UBE2V2	XM_017013808.3	c.310C>A	p.Pro104Thr	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>A	p.Pro77Thr	missense_variant	Exon 3 of 4	1	NM_003350.3	ENSP00000428209.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1432738 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 712756

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.08e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Benign	-0.0048	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.53	D;T;T;T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Pathogenic	0.98	D;.;.;D
M_CAP	Benign	0.040	D
MetaRNN	Pathogenic	0.74	D;D;D;D
MetaSVM	Uncertain	0.28	D
MutationAssessor	Pathogenic	4.2	H;.;.;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-6.2	D;D;D;D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D
Polyphen		0.97	D;.;.;.
Vest4		0.57
MutPred		0.79		Loss of ubiquitination at K72 (P = 0.0672);.;.;.;
MVP		0.90
MPC		1.6
ClinPred		1.0	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.90
gMVP		0.63

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: chr8-48962476;