7-49775598-G-T

Position:

• chr7-49775598-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198570.5(VWC2):​c.163G>T​(p.Gly55Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000724 in 1,381,628 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: VWC2 NM_198570.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.37

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]

ACMG classification

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=0.088178754).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VWC2	NM_198570.5	c.163G>T	p.Gly55Cys	missense_variant	2/4	ENST00000340652.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VWC2	ENST00000340652.5	c.163G>T	p.Gly55Cys	missense_variant	2/4	1	NM_198570.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.24e-7 AC: 1 AN: 1381628 Hom.: 0 Cov.: 44 AF XY: 0.00000147 AC XY: 1 AN XY: 681462

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: 0.0000129

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 06, 2024

The c.163G>T (p.G55C) alteration is located in exon 2 (coding exon 1) of the VWC2 gene. This alteration results from a G to T substitution at nucleotide position 163, causing the glycine (G) at amino acid position 55 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	0.22
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0056	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
MutationTaster	Benign	0.99	N
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.13
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.0	B
Vest4		0.19
MutPred		0.16		Loss of methylation at R58 (P = 0.0715);
MVP		0.043
MPC		1.7
ClinPred		0.67	D
GERP RS		-0.88
Varity_R		0.15
gMVP		0.45

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-49815194;