chr3-184230590-G-C

Variant summary

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

The NM_001390846.1(VWA5B2):ā€‹c.62G>Cā€‹(p.Arg21Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000212 in 1,463,530 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000053 ( 0 hom., cov: 33)
Exomes š‘“: 0.000018 ( 0 hom. )

Consequence

VWA5B2
NM_001390846.1 missense

Scores

3
5
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.78
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
VWA5B2NM_001390846.1 linkuse as main transcriptc.62G>C p.Arg21Pro missense_variant 2/20 ENST00000691901.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
VWA5B2ENST00000691901.1 linkuse as main transcriptc.62G>C p.Arg21Pro missense_variant 2/20 NM_001390846.1 P1
VWA5B2ENST00000426955.6 linkuse as main transcriptc.62G>C p.Arg21Pro missense_variant 1/191 P1

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152082
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000386
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.0000287
AC:
2
AN:
69656
Hom.:
0
AF XY:
0.0000247
AC XY:
1
AN XY:
40528
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000744
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000398
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000175
AC:
23
AN:
1311448
Hom.:
0
Cov.:
30
AF XY:
0.0000201
AC XY:
13
AN XY:
646646
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000404
Gnomad4 ASJ exome
AF:
0.0000435
Gnomad4 EAS exome
AF:
0.000144
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000287
Gnomad4 OTH exome
AF:
0.000258
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152082
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74296
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.000479
Bravo
AF:
0.0000491
Asia WGS
AF:
0.000291
AC:
1
AN:
3452

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 09, 2024The c.62G>C (p.R21P) alteration is located in exon 1 (coding exon 1) of the VWA5B2 gene. This alteration results from a G to C substitution at nucleotide position 62, causing the arginine (R) at amino acid position 21 to be replaced by a proline (P). 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
Pathogenic
0.83
BayesDel_addAF
Benign
0.0062
T
BayesDel_noAF
Benign
-0.23
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Benign
0.015
T
Eigen
Uncertain
0.38
Eigen_PC
Uncertain
0.36
FATHMM_MKL
Benign
0.57
D
LIST_S2
Benign
0.85
T
M_CAP
Pathogenic
0.76
D
MetaRNN
Uncertain
0.42
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.4
L
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.89
D
PROVEAN
Benign
-1.3
N
REVEL
Benign
0.21
Sift
Benign
0.11
T
Sift4G
Uncertain
0.042
D
Vest4
0.39
MutPred
0.56
Loss of catalytic residue at R21 (P = 0.0231);
MVP
0.30
MPC
1.9
ClinPred
0.35
T
GERP RS
4.0
Varity_R
0.42
gMVP
0.82

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: rs929455841; hg19: chr3-183948378; API