rs10499687

Variant names:

• chr7-49794092-C-T
• rs10499687
• NM_198570.5:c.697-8619C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198570.5(VWC2):​c.697-8619C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,174 control chromosomes in the GnomAD database, including 946 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (946 hom., cov: 32)
• Consequence: VWC2 NM_198570.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWC2	NM_198570.5	c.697-8619C>T		intron_variant	Intron 2 of 3	ENST00000340652.5	NP_940972.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWC2	ENST00000340652.5	c.697-8619C>T		intron_variant	Intron 2 of 3	1	NM_198570.5	ENSP00000341819.3

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16382 AN: 152056 Hom.: 946 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0971

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0810

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.100

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.108 AC: 16402 AN: 152174 Hom.: 946 Cov.: 32 AF XY: 0.107 AC XY: 7969 AN XY: 74416

African (AFR) AF: 0.123 AC: 5105 AN: 41518

American (AMR) AF: 0.108 AC: 1654 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0971 AC: 337 AN: 3470

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5184

South Asian (SAS) AF: 0.0807 AC: 389 AN: 4822

European-Finnish (FIN) AF: 0.142 AC: 1507 AN: 10590

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7108 AN: 67984

Other (OTH) AF: 0.0988 AC: 209 AN: 2116

Alfa AF: 0.100 Hom.: 2682

Bravo AF: 0.104

Asia WGS AF: 0.0380 AC: 132 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.5
DANN	Benign	0.40
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10499687; hg19: chr7-49833688;