GeneBe

rs1717765685

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_001390846.1(VWA5B2):​c.822G>A​(p.Glu274Glu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000429 in 1,398,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

VWA5B2
NM_001390846.1 splice_region, synonymous

Scores

2
Splicing: ADA: 0.01379
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.853
Variant links:
Genes affected
VWA5B2 (HGNC:25144): (von Willebrand factor A domain containing 5B2)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP7
Synonymous conserved (PhyloP=0.853 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
VWA5B2NM_001390846.1 linkc.822G>A p.Glu274Glu splice_region_variant, synonymous_variant Exon 7 of 20 ENST00000691901.1 NP_001377775.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
VWA5B2ENST00000691901.1 linkc.822G>A p.Glu274Glu splice_region_variant, synonymous_variant Exon 7 of 20 NM_001390846.1 ENSP00000509115.1 Q8N398

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000429
AC:
6
AN:
1398836
Hom.:
0
Cov.:
32
AF XY:
0.00000145
AC XY:
1
AN XY:
689904
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
31590
American (AMR)
AF:
0.00
AC:
0
AN:
35664
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25172
East Asian (EAS)
AF:
0.00
AC:
0
AN:
35738
South Asian (SAS)
AF:
0.00
AC:
0
AN:
79222
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
48898
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5678
European-Non Finnish (NFE)
AF:
0.00000463
AC:
5
AN:
1078894
Other (OTH)
AF:
0.0000172
AC:
1
AN:
57980
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.517
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.00
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.39
CADD
Benign
12
DANN
Benign
0.86
PhyloP100
0.85

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.014
dbscSNV1_RF
Benign
0.17
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

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Other links and lift over

dbSNP: rs1717765685; hg19: chr3-183952420; COSMIC: COSV104563372; COSMIC: COSV104563372; API