3-184233349-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001390846.1(VWA5B2):​c.482C>T​(p.Pro161Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000779 in 1,539,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000072 ( 0 hom. )

Consequence

VWA5B2
NM_001390846.1 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.247
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.041163653).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
VWA5B2NM_001390846.1 linkuse as main transcriptc.482C>T p.Pro161Leu missense_variant 4/20 ENST00000691901.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
VWA5B2ENST00000691901.1 linkuse as main transcriptc.482C>T p.Pro161Leu missense_variant 4/20 NM_001390846.1 P1
VWA5B2ENST00000426955.6 linkuse as main transcriptc.482C>T p.Pro161Leu missense_variant 3/191 P1
VWA5B2ENST00000497229.1 linkuse as main transcriptn.750C>T non_coding_transcript_exon_variant 1/32

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152234
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000146
AC:
2
AN:
137268
Hom.:
0
AF XY:
0.0000273
AC XY:
2
AN XY:
73360
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000979
Gnomad SAS exome
AF:
0.0000477
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000721
AC:
10
AN:
1387320
Hom.:
0
Cov.:
33
AF XY:
0.00000439
AC XY:
3
AN XY:
683776
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000281
Gnomad4 SAS exome
AF:
0.0000258
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000558
Gnomad4 OTH exome
AF:
0.0000174
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152234
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74370
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.066
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
14
DANN
Benign
0.85
DEOGEN2
Benign
0.0029
T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.093
N
LIST_S2
Benign
0.70
T
M_CAP
Benign
0.0074
T
MetaRNN
Benign
0.041
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.7
L
MutationTaster
Benign
0.98
D;N
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-1.9
N
REVEL
Benign
0.021
Sift
Benign
0.046
D
Sift4G
Benign
0.13
T
Vest4
0.093
MutPred
0.25
Loss of glycosylation at P161 (P = 0.0113);
MVP
0.040
MPC
0.62
ClinPred
0.026
T
GERP RS
-2.6
Varity_R
0.050
gMVP
0.42

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: rs1296285612; hg19: chr3-183951137; COSMIC: COSV99891671; COSMIC: COSV99891671; API