chr3-184234310-C-A

Variant summary

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

The NM_001390846.1(VWA5B2):​c.733C>A​(p.His245Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 (★).

Frequency

Genomes: not found (cov: 33)

Consequence

VWA5B2
NM_001390846.1 missense

Scores

2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.44
Variant links:
Genes affected
VWA5B2 (HGNC:25144): (von Willebrand factor A domain containing 5B2)

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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=0.05058229).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
VWA5B2NM_001390846.1 linkuse as main transcriptc.733C>A p.His245Asn missense_variant 6/20 ENST00000691901.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
VWA5B2ENST00000691901.1 linkuse as main transcriptc.733C>A p.His245Asn missense_variant 6/20 NM_001390846.1 P1
VWA5B2ENST00000426955.6 linkuse as main transcriptc.733C>A p.His245Asn missense_variant 5/191 P1
VWA5B2ENST00000273794.5 linkuse as main transcriptc.76C>A p.His26Asn missense_variant 3/172
VWA5B2ENST00000497229.1 linkuse as main transcriptn.1179C>A non_coding_transcript_exon_variant 2/32

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

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 GeneticsSep 01, 2021The c.733C>A (p.H245N) alteration is located in exon 5 (coding exon 5) of the VWA5B2 gene. This alteration results from a C to A substitution at nucleotide position 733, causing the histidine (H) at amino acid position 245 to be replaced by an asparagine (N). 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
0.11
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0056
.;T
Eigen
Benign
-0.34
Eigen_PC
Benign
-0.24
FATHMM_MKL
Benign
0.16
N
LIST_S2
Benign
0.79
T;T
M_CAP
Benign
0.0051
T
MetaRNN
Benign
0.051
T;T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
0.66
N;N;N
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-0.73
N;N
REVEL
Benign
0.027
Sift
Benign
0.30
T;T
Sift4G
Benign
0.41
T;T
Polyphen
0.035
.;B
Vest4
0.21
MutPred
0.18
.;Loss of glycosylation at P25 (P = 0.0454);
MVP
0.061
MPC
1.1
ClinPred
0.22
T
GERP RS
3.9
Varity_R
0.093
gMVP
0.48

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-183952098; API