rs6963083

Positions:

• chr7-49869855-G-A
• chr7-49869855-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198570.5(VWC2):​c.827-42179G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 151,772 control chromosomes in the GnomAD database, including 35,204 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 0.67 (35204 hom., cov: 31)
• Consequence: VWC2 NM_198570.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26

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]

ZPBP (HGNC:15662): (zona pellucida binding protein) ZPBP is one of several proteins that are thought to participate in secondary binding between acrosome-reacted sperm and the egg-specific extracellular matrix, the zona pellucida (McLeskey et al., 1998 [PubMed 9378618]).[supplied by OMIM, Aug 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWC2	NM_198570.5	c.827-42179G>A		intron_variant		ENST00000340652.5	NP_940972.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWC2	ENST00000340652.5	c.827-42179G>A		intron_variant		1	NM_198570.5	ENSP00000341819	P1
ZPBP	ENST00000465922.1	n.510-19341C>T		intron_variant, non_coding_transcript_variant		4
ZPBP	ENST00000491129.5	n.517-19341C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102052 AN: 151654 Hom.: 35193 Cov.: 31

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.831

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.656

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

GnomAD4 genome AF: 0.673 AC: 102105 AN: 151772 Hom.: 35204 Cov.: 31 AF XY: 0.675 AC XY: 50058 AN XY: 74144

Gnomad4 AFR AF: 0.529

Gnomad4 AMR AF: 0.610

Gnomad4 ASJ AF: 0.667

Gnomad4 EAS AF: 0.883

Gnomad4 SAS AF: 0.568

Gnomad4 FIN AF: 0.802

Gnomad4 NFE AF: 0.744

Gnomad4 OTH AF: 0.655

Alfa AF: 0.721 Hom.: 80457

Bravo AF: 0.654

Asia WGS AF: 0.660 AC: 2293 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.4
DANN	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs6963083; hg19: chr7-49909451;