3-184233677-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.632C>T​(p.Pro211Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000267 in 1,551,334 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 0.00027 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

VWA5B2
NM_001390846.1 missense

Scores

3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.56
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=0.049275964).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
VWA5B2NM_001390846.1 linkuse as main transcriptc.632C>T p.Pro211Leu missense_variant 5/20 ENST00000691901.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
VWA5B2ENST00000691901.1 linkuse as main transcriptc.632C>T p.Pro211Leu missense_variant 5/20 NM_001390846.1 P1
VWA5B2ENST00000426955.6 linkuse as main transcriptc.632C>T p.Pro211Leu missense_variant 4/191 P1
VWA5B2ENST00000273794.5 linkuse as main transcriptc.-26C>T 5_prime_UTR_variant 2/172
VWA5B2ENST00000497229.1 linkuse as main transcriptn.1078C>T non_coding_transcript_exon_variant 1/32

Frequencies

GnomAD3 genomes
AF:
0.000269
AC:
41
AN:
152214
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000393
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:
0.000441
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.000189
AC:
29
AN:
153362
Hom.:
0
AF XY:
0.000209
AC XY:
17
AN XY:
81432
show subpopulations
Gnomad AFR exome
AF:
0.000253
Gnomad AMR exome
AF:
0.000243
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:
0.000323
Gnomad OTH exome
AF:
0.000460
GnomAD4 exome
AF:
0.000267
AC:
373
AN:
1399002
Hom.:
0
Cov.:
32
AF XY:
0.000233
AC XY:
161
AN XY:
690038
show subpopulations
Gnomad4 AFR exome
AF:
0.0000633
Gnomad4 AMR exome
AF:
0.000252
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000204
Gnomad4 NFE exome
AF:
0.000324
Gnomad4 OTH exome
AF:
0.000190
GnomAD4 genome
AF:
0.000269
AC:
41
AN:
152332
Hom.:
0
Cov.:
32
AF XY:
0.000242
AC XY:
18
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.0000722
Gnomad4 AMR
AF:
0.000392
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000441
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.000326
Hom.:
0
Bravo
AF:
0.000219
TwinsUK
AF:
0.000539
AC:
2
ALSPAC
AF:
0.000778
AC:
3
ExAC
AF:
0.0000364
AC:
2

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 GeneticsJul 14, 2022The c.632C>T (p.P211L) alteration is located in exon 4 (coding exon 4) of the VWA5B2 gene. This alteration results from a C to T substitution at nucleotide position 632, causing the proline (P) at amino acid position 211 to be replaced by a leucine (L). 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
0.12
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.49
CADD
Uncertain
23
DANN
Benign
0.85
DEOGEN2
Benign
0.0016
T
Eigen
Benign
0.11
Eigen_PC
Benign
0.17
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Benign
0.80
T
M_CAP
Benign
0.0092
T
MetaRNN
Benign
0.049
T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.74
T
PROVEAN
Uncertain
-3.8
D
REVEL
Benign
0.078
Sift
Benign
0.15
T
Sift4G
Benign
0.72
T
Vest4
0.17
MVP
0.33
MPC
0.75
ClinPred
0.044
T
GERP RS
3.8
Varity_R
0.15
gMVP
0.39

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: rs571169902; hg19: chr3-183951465; API