NM_022834.5:c.94C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022834.5(VWA1):ā€‹c.94C>Gā€‹(p.Arg32Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000249 in 1,607,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

VWA1
NM_022834.5 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.30
Variant links:
Genes affected
VWA1 (HGNC:30910): (von Willebrand factor A domain containing 1) VWA1 belongs to the von Willebrand factor (VWF; MIM 613160) A (VWFA) domain superfamily of extracellular matrix proteins and appears to play a role in cartilage structure and function (Fitzgerald et al., 2002 [PubMed 12062410]).[supplied by OMIM, Nov 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07145396).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
VWA1NM_022834.5 linkc.94C>G p.Arg32Gly missense_variant Exon 2 of 3 ENST00000476993.2 NP_073745.2 Q6PCB0-1
VWA1NM_199121.3 linkc.74-375C>G intron_variant Intron 1 of 2 NP_954572.2 Q6PCB0-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
VWA1ENST00000476993.2 linkc.94C>G p.Arg32Gly missense_variant Exon 2 of 3 1 NM_022834.5 ENSP00000417185.1 Q6PCB0-1
VWA1ENST00000471398.1 linkc.214C>G p.Arg72Gly missense_variant Exon 2 of 2 3 ENSP00000464343.1 J3QRR0
VWA1ENST00000495558 linkc.-12C>G 5_prime_UTR_variant Exon 2 of 2 2 ENSP00000463643.1 J3QLP3
VWA1ENST00000338660.5 linkc.74-375C>G intron_variant Intron 1 of 2 2 ENSP00000423404.1 Q6PCB0-3

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152216
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1455278
Hom.:
0
Cov.:
31
AF XY:
0.00000277
AC XY:
2
AN XY:
723194
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152216
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74368
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000101
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.060
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
19
DANN
Benign
0.86
DEOGEN2
Benign
0.13
T;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.084
N
LIST_S2
Benign
0.39
T;T
M_CAP
Benign
0.064
D
MetaRNN
Benign
0.071
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.0
N;.
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
-1.1
N;.
REVEL
Benign
0.014
Sift
Benign
0.055
T;.
Sift4G
Benign
0.093
T;T
Polyphen
0.0010
B;.
Vest4
0.12
MutPred
0.31
Gain of glycosylation at S29 (P = 0.0719);.;
MVP
0.27
MPC
0.039
ClinPred
0.052
T
GERP RS
1.7
Varity_R
0.087
gMVP
0.43

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs762573767; hg19: chr1-1372327; API