3-184230857-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001390846.1(VWA5B2):​c.250G>T​(p.Ala84Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000152 in 1,241,780 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00016 ( 1 hom. )

Consequence

VWA5B2
NM_001390846.1 missense

Scores

2
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.05
Variant links:
Genes affected
VWA5B2 (HGNC:25144): (von Willebrand factor A domain containing 5B2)

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.12302503).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
VWA5B2NM_001390846.1 linkuse as main transcriptc.250G>T p.Ala84Ser missense_variant 3/20 ENST00000691901.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
VWA5B2ENST00000691901.1 linkuse as main transcriptc.250G>T p.Ala84Ser missense_variant 3/20 NM_001390846.1 P1
VWA5B2ENST00000426955.6 linkuse as main transcriptc.250G>T p.Ala84Ser missense_variant 2/191 P1

Frequencies

GnomAD3 genomes
AF:
0.000106
AC:
16
AN:
151656
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000460
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.000480
GnomAD4 exome
AF:
0.000159
AC:
173
AN:
1090016
Hom.:
1
Cov.:
30
AF XY:
0.000142
AC XY:
74
AN XY:
519798
show subpopulations
Gnomad4 AFR exome
AF:
0.0000447
Gnomad4 AMR exome
AF:
0.00107
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:
0.000171
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.000105
AC:
16
AN:
151764
Hom.:
0
Cov.:
33
AF XY:
0.000108
AC XY:
8
AN XY:
74190
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000460
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.000475
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.000200

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 20, 2024The c.250G>T (p.A84S) alteration is located in exon 2 (coding exon 2) of the VWA5B2 gene. This alteration results from a G to T substitution at nucleotide position 250, causing the alanine (A) at amino acid position 84 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
Benign
0.085
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
18
DANN
Uncertain
0.97
DEOGEN2
Benign
0.0017
T
Eigen
Benign
-0.43
Eigen_PC
Benign
-0.24
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Benign
0.72
T
M_CAP
Pathogenic
0.62
D
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.12
N
MutationTaster
Benign
1.0
D;N
PrimateAI
Pathogenic
0.86
D
PROVEAN
Benign
-0.010
N
REVEL
Benign
0.047
Sift
Benign
0.49
T
Sift4G
Benign
0.15
T
Vest4
0.13
MutPred
0.23
Loss of helix (P = 0.028);
MVP
0.055
MPC
0.56
ClinPred
0.18
T
GERP RS
3.0
Varity_R
0.089
gMVP
0.35

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs942998005; hg19: chr3-183948645; API