chr3-184230590-G-C
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001390846.1(VWA5B2):āc.62G>Cā(p.Arg21Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000212 in 1,463,530 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000053 ( 0 hom., cov: 33)
Exomes š: 0.000018 ( 0 hom. )
Consequence
VWA5B2
NM_001390846.1 missense
NM_001390846.1 missense
Scores
3
5
11
Clinical Significance
Conservation
PhyloP100: 1.78
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VWA5B2 | NM_001390846.1 | c.62G>C | p.Arg21Pro | missense_variant | 2/20 | ENST00000691901.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VWA5B2 | ENST00000691901.1 | c.62G>C | p.Arg21Pro | missense_variant | 2/20 | NM_001390846.1 | P1 | ||
VWA5B2 | ENST00000426955.6 | c.62G>C | p.Arg21Pro | missense_variant | 1/19 | 1 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152082Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000287 AC: 2AN: 69656Hom.: 0 AF XY: 0.0000247 AC XY: 1AN XY: 40528
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GnomAD4 exome AF: 0.0000175 AC: 23AN: 1311448Hom.: 0 Cov.: 30 AF XY: 0.0000201 AC XY: 13AN XY: 646646
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GnomAD4 genome AF: 0.0000526 AC: 8AN: 152082Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74296
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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 | Jan 09, 2024 | The c.62G>C (p.R21P) alteration is located in exon 1 (coding exon 1) of the VWA5B2 gene. This alteration results from a G to C substitution at nucleotide position 62, causing the arginine (R) at amino acid position 21 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Uncertain
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Uncertain
D
Vest4
MutPred
Loss of catalytic residue at R21 (P = 0.0231);
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