3-184233700-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001390846.1(VWA5B2):​c.655G>A​(p.Glu219Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000967 in 1,550,936 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: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

VWA5B2
NM_001390846.1 missense

Scores

1
7
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.01
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3560552).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
VWA5B2NM_001390846.1 linkuse as main transcriptc.655G>A p.Glu219Lys missense_variant 5/20 ENST00000691901.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
VWA5B2ENST00000691901.1 linkuse as main transcriptc.655G>A p.Glu219Lys missense_variant 5/20 NM_001390846.1 P1
VWA5B2ENST00000426955.6 linkuse as main transcriptc.655G>A p.Glu219Lys missense_variant 4/191 P1
VWA5B2ENST00000273794.5 linkuse as main transcriptc.-3G>A 5_prime_UTR_variant 2/172
VWA5B2ENST00000497229.1 linkuse as main transcriptn.1101G>A non_coding_transcript_exon_variant 1/32

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152188
Hom.:
0
Cov.:
32
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:
0.000193
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
GnomAD3 exomes
AF:
0.0000262
AC:
4
AN:
152940
Hom.:
0
AF XY:
0.0000246
AC XY:
2
AN XY:
81252
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000184
Gnomad SAS exome
AF:
0.0000439
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000171
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000100
AC:
14
AN:
1398748
Hom.:
0
Cov.:
32
AF XY:
0.00000870
AC XY:
6
AN XY:
689908
show subpopulations
Gnomad4 AFR exome
AF:
0.0000317
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000280
Gnomad4 SAS exome
AF:
0.0000126
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000927
Gnomad4 OTH exome
AF:
0.0000173
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152188
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000306
Hom.:
0

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 GeneticsNov 22, 2023The c.655G>A (p.E219K) alteration is located in exon 4 (coding exon 4) of the VWA5B2 gene. This alteration results from a G to A substitution at nucleotide position 655, causing the glutamic acid (E) at amino acid position 219 to be replaced by a lysine (K). 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
-0.19
T
BayesDel_noAF
Benign
-0.23
CADD
Pathogenic
26
DANN
Uncertain
1.0
Eigen
Uncertain
0.21
Eigen_PC
Uncertain
0.28
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.88
D
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.36
T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
1.0
D;D;N
PrimateAI
Pathogenic
0.89
D
PROVEAN
Benign
-1.6
N
REVEL
Benign
0.16
Sift
Uncertain
0.015
D
Sift4G
Benign
0.064
T
Vest4
0.57
MutPred
0.49
Gain of ubiquitination at E219 (P = 0.0219);
MVP
0.14
MPC
1.1
ClinPred
0.34
T
GERP RS
3.9
Varity_R
0.23
gMVP
0.50

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs866076856; hg19: chr3-183951488; COSMIC: COSV104563405; COSMIC: COSV104563405; API