chr7-49775473-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_198570.5(VWC2):ā€‹c.38C>Gā€‹(p.Ser13Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000145 in 1,381,056 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

VWC2
NM_198570.5 missense

Scores

2
7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.54
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]

Genome browser will be placed here

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 Protein UniProt
VWC2NM_198570.5 linkc.38C>G p.Ser13Cys 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.38C>G p.Ser13Cys missense_variant 2/41 NM_198570.5 ENSP00000341819.3 Q2TAL6

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000145
AC:
2
AN:
1381056
Hom.:
0
Cov.:
44
AF XY:
0.00000292
AC XY:
2
AN XY:
684272
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000613
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:
0.0000151
ExAC
AF:
0.00000833
AC:
1

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 GeneticsOct 25, 2024The c.38C>G (p.S13C) alteration is located in exon 2 (coding exon 1) of the VWC2 gene. This alteration results from a C to G substitution at nucleotide position 38, causing the serine (S) at amino acid position 13 to be replaced by a cysteine (C). 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
0.16
BayesDel_addAF
Benign
-0.060
T
BayesDel_noAF
Benign
-0.32
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0058
T
Eigen
Uncertain
0.29
Eigen_PC
Uncertain
0.37
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.72
T
M_CAP
Uncertain
0.26
D
MetaRNN
Uncertain
0.47
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
1.0
L
PrimateAI
Pathogenic
0.91
D
PROVEAN
Benign
-0.93
N
REVEL
Benign
0.17
Sift
Uncertain
0.0020
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.97
D
Vest4
0.66
MutPred
0.30
Loss of loop (P = 0.0288);
MVP
0.043
MPC
2.1
ClinPred
0.66
D
GERP RS
4.7
Varity_R
0.34
gMVP
0.40

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: rs745920342; hg19: chr7-49815069; API