chr3-184230629-G-A

Variant summary

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

The NM_001390846.1(VWA5B2):​c.101G>A​(p.Arg34Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000143 in 1,400,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 8.0e-7 ( 0 hom. )

Consequence

VWA5B2
NM_001390846.1 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.80
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=0.14822963).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
VWA5B2NM_001390846.1 linkuse as main transcriptc.101G>A p.Arg34Gln missense_variant 2/20 ENST00000691901.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
VWA5B2ENST00000691901.1 linkuse as main transcriptc.101G>A p.Arg34Gln missense_variant 2/20 NM_001390846.1 P1
VWA5B2ENST00000426955.6 linkuse as main transcriptc.101G>A p.Arg34Gln missense_variant 1/191 P1

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151984
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000194
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
8.01e-7
AC:
1
AN:
1249008
Hom.:
0
Cov.:
30
AF XY:
0.00000163
AC XY:
1
AN XY:
613436
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000366
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
151984
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74244
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000194
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113

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 GeneticsJan 31, 2024The c.101G>A (p.R34Q) alteration is located in exon 1 (coding exon 1) of the VWA5B2 gene. This alteration results from a G to A substitution at nucleotide position 101, causing the arginine (R) at amino acid position 34 to be replaced by a glutamine (Q). 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
0.10
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.55
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0021
T
Eigen
Benign
0.030
Eigen_PC
Benign
0.13
FATHMM_MKL
Benign
0.39
N
LIST_S2
Benign
0.85
D
M_CAP
Pathogenic
0.45
D
MetaRNN
Benign
0.15
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.20
N
MutationTaster
Benign
1.0
D;N
PrimateAI
Uncertain
0.75
T
PROVEAN
Benign
0.19
N
REVEL
Benign
0.052
Sift
Benign
0.38
T
Sift4G
Benign
0.065
T
Vest4
0.14
MutPred
0.44
Loss of methylation at R34 (P = 0.0306);
MVP
0.076
MPC
0.89
ClinPred
0.54
D
GERP RS
4.0
Varity_R
0.082
gMVP
0.37

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: rs1468229019; hg19: chr3-183948417; API