chr7-49775862-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_198570.5(VWC2):​c.427G>A​(p.Glu143Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

VWC2
NM_198570.5 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.79
Variant links:
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]

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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=0.30997562).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
VWC2NM_198570.5 linkc.427G>A p.Glu143Lys missense_variant 2/4 ENST00000340652.5 NP_940972.2 Q2TAL6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
VWC2ENST00000340652.5 linkc.427G>A p.Glu143Lys missense_variant 2/41 NM_198570.5 ENSP00000341819.3 Q2TAL6

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1403194
Hom.:
0
Cov.:
36
AF XY:
0.00
AC XY:
0
AN XY:
692822
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

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 submitterclinical testingAmbry GeneticsDec 10, 2024The c.427G>A (p.E143K) 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 427, causing the glutamic acid (E) at amino acid position 143 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Benign
-0.054
T
BayesDel_noAF
Benign
-0.31
CADD
Pathogenic
31
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.0074
T
Eigen
Uncertain
0.46
Eigen_PC
Uncertain
0.52
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.85
T
M_CAP
Uncertain
0.088
D
MetaRNN
Benign
0.31
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.0
L
PrimateAI
Uncertain
0.75
T
PROVEAN
Benign
-1.3
N
REVEL
Benign
0.19
Sift
Uncertain
0.0080
D
Sift4G
Uncertain
0.012
D
Polyphen
1.0
D
Vest4
0.29
MutPred
0.41
Gain of ubiquitination at E143 (P = 0.0029);
MVP
0.12
MPC
2.1
ClinPred
0.94
D
GERP RS
5.3
Varity_R
0.31
gMVP
0.34

Splicing

Name
Calibrated prediction
Score
Prediction
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

LitVar

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

Other links and lift over

dbSNP: rs747070555; hg19: chr7-49815458; API