chr3-184234751-G-A

Variant summary

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

The NM_001390846.1(VWA5B2):​c.941G>A​(p.Arg314Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000838 in 1,550,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R314W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

VWA5B2
NM_001390846.1 missense

Scores

5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.49
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=0.052801877).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
VWA5B2NM_001390846.1 linkuse as main transcriptc.941G>A p.Arg314Gln missense_variant 7/20 ENST00000691901.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
VWA5B2ENST00000691901.1 linkuse as main transcriptc.941G>A p.Arg314Gln missense_variant 7/20 NM_001390846.1 P1

Frequencies

GnomAD3 genomes
AF:
0.000158
AC:
24
AN:
152212
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000169
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:
0.000188
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000206
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000586
AC:
9
AN:
153546
Hom.:
0
AF XY:
0.0000367
AC XY:
3
AN XY:
81836
show subpopulations
Gnomad AFR exome
AF:
0.000138
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000119
Gnomad NFE exome
AF:
0.000103
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000751
AC:
105
AN:
1398206
Hom.:
0
Cov.:
32
AF XY:
0.0000667
AC XY:
46
AN XY:
689634
show subpopulations
Gnomad4 AFR exome
AF:
0.0000633
Gnomad4 AMR exome
AF:
0.0000280
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000114
Gnomad4 FIN exome
AF:
0.000124
Gnomad4 NFE exome
AF:
0.0000742
Gnomad4 OTH exome
AF:
0.000121
GnomAD4 genome
AF:
0.000164
AC:
25
AN:
152330
Hom.:
0
Cov.:
33
AF XY:
0.000188
AC XY:
14
AN XY:
74498
show subpopulations
Gnomad4 AFR
AF:
0.000192
Gnomad4 AMR
AF:
0.0000653
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.000206
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000959
Hom.:
0
Bravo
AF:
0.000117
ExAC
AF:
0.0000449
AC:
1

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 GeneticsJun 10, 2024The c.941G>A (p.R314Q) alteration is located in exon 6 (coding exon 6) of the VWA5B2 gene. This alteration results from a G to A substitution at nucleotide position 941, causing the arginine (R) at amino acid position 314 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
0.079
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.096
.;T
Eigen
Benign
-0.032
Eigen_PC
Benign
0.070
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Benign
0.80
T;T
M_CAP
Benign
0.0053
T
MetaRNN
Benign
0.053
T;T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Benign
0.31
T
PROVEAN
Uncertain
-2.6
D;D
REVEL
Benign
0.051
Sift
Uncertain
0.022
D;D
Sift4G
Uncertain
0.012
D;D
Polyphen
0.13
.;B
Vest4
0.12
MVP
0.092
MPC
0.73
ClinPred
0.17
T
GERP RS
4.0
Varity_R
0.39
gMVP
0.41

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: rs752607575; hg19: chr3-183952539; COSMIC: COSV56610937; COSMIC: COSV56610937; API