7-49776100-G-A
Position:
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_198570.5(VWC2):c.665G>A(p.Gly222Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000841 in 1,546,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000086 ( 0 hom. )
Consequence
VWC2
NM_198570.5 missense
NM_198570.5 missense
Scores
6
10
3
Clinical Significance
Conservation
PhyloP100: 6.74
Genes affected
VWC2 (HGNC:30200): (von Willebrand factor C domain containing 2) This gene encodes a secreted bone morphogenic protein antagonist. The encoded protein is possibly involved in neural function and development and may have a role in cell adhesion.[provided by RefSeq, Oct 2009]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.875
BS2
High AC in GnomAdExome4 at 12 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VWC2 | NM_198570.5 | c.665G>A | p.Gly222Asp | missense_variant | 2/4 | ENST00000340652.5 | NP_940972.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
VWC2 | ENST00000340652.5 | c.665G>A | p.Gly222Asp | missense_variant | 2/4 | 1 | NM_198570.5 | ENSP00000341819 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152272Hom.: 0 Cov.: 33
GnomAD3 genomes
AF:
AC:
1
AN:
152272
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000861 AC: 12AN: 1394100Hom.: 0 Cov.: 36 AF XY: 0.00000727 AC XY: 5AN XY: 687946
GnomAD4 exome
AF:
AC:
12
AN:
1394100
Hom.:
Cov.:
36
AF XY:
AC XY:
5
AN XY:
687946
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152272Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74398
GnomAD4 genome
AF:
AC:
1
AN:
152272
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
74398
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
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 | Feb 28, 2023 | The c.665G>A (p.G222D) alteration is located in exon 2 (coding exon 1) of the VWC2 gene. This alteration results from a G to A substitution at nucleotide position 665, causing the glycine (G) at amino acid position 222 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
P
Vest4
MutPred
Gain of ubiquitination at K223 (P = 0.0527);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at