7-49902109-T-C

Variant names:

• chr7-49902109-T-C
• rs1532989
• NM_198570.5:c.827-9925T>C

Variant summary

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

The NM_198570.5(VWC2):​c.827-9925T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 151,700 control chromosomes in the GnomAD database, including 41,359 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 0.74 (41359 hom., cov: 31)
• Consequence: VWC2 NM_198570.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.208
• Publications: 1 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]

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]

ZPBP Gene-Disease associations (from GenCC):

• spermatogenic failure 66

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198570.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWC2	NM_198570.5	MANE Select	c.827-9925T>C		intron	N/A	NP_940972.2
	VWC2	NR_136188.1		n.930-9925T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWC2	ENST00000340652.5	TSL:1 MANE Select	c.827-9925T>C		intron	N/A	ENSP00000341819.3
	ZPBP	ENST00000465922.1	TSL:4	n.412-894A>G		intron	N/A
	ZPBP	ENST00000491129.5	TSL:3	n.419-894A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.737 AC: 111660 AN: 151582 Hom.: 41340 Cov.: 31

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.831

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.885

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.816

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.755

Gnomad OTH AF: 0.717

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

GnomAD4 genome AF: 0.737 AC: 111732 AN: 151700 Hom.: 41359 Cov.: 31 AF XY: 0.739 AC XY: 54785 AN XY: 74110

African (AFR) AF: 0.707 AC: 29313 AN: 41432

American (AMR) AF: 0.649 AC: 9893 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.695 AC: 2409 AN: 3464

East Asian (EAS) AF: 0.885 AC: 4565 AN: 5158

South Asian (SAS) AF: 0.697 AC: 3354 AN: 4812

European-Finnish (FIN) AF: 0.816 AC: 8619 AN: 10562

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.755 AC: 51093 AN: 67712

Other (OTH) AF: 0.716 AC: 1508 AN: 2106

Alfa AF: 0.722 Hom.: 6217

Bravo AF: 0.722

Asia WGS AF: 0.734 AC: 2546 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.8
DANN	Benign	0.78
PhyloP100		0.21
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: rs1532989; hg19: chr7-49941705;