3-184233700-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001390846.1(VWA5B2):c.655G>A(p.Glu219Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000967 in 1,550,936 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
VWA5B2
NM_001390846.1 missense
NM_001390846.1 missense
Scores
1
7
9
Clinical Significance
Conservation
PhyloP100: 6.01
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3560552).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VWA5B2 | NM_001390846.1 | c.655G>A | p.Glu219Lys | missense_variant | 5/20 | ENST00000691901.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VWA5B2 | ENST00000691901.1 | c.655G>A | p.Glu219Lys | missense_variant | 5/20 | NM_001390846.1 | P1 | ||
VWA5B2 | ENST00000426955.6 | c.655G>A | p.Glu219Lys | missense_variant | 4/19 | 1 | P1 | ||
VWA5B2 | ENST00000273794.5 | c.-3G>A | 5_prime_UTR_variant | 2/17 | 2 | ||||
VWA5B2 | ENST00000497229.1 | n.1101G>A | non_coding_transcript_exon_variant | 1/3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152188Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000262 AC: 4AN: 152940Hom.: 0 AF XY: 0.0000246 AC XY: 2AN XY: 81252
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GnomAD4 exome AF: 0.0000100 AC: 14AN: 1398748Hom.: 0 Cov.: 32 AF XY: 0.00000870 AC XY: 6AN XY: 689908
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152188Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74346
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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 submitter | clinical testing | Ambry Genetics | Nov 22, 2023 | The c.655G>A (p.E219K) alteration is located in exon 4 (coding exon 4) of the VWA5B2 gene. This alteration results from a G to A substitution at nucleotide position 655, causing the glutamic acid (E) at amino acid position 219 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;N
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Benign
T
Vest4
MutPred
Gain of ubiquitination at E219 (P = 0.0219);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at