20-45477098-C-G

Position:

• chr20-45477098-C-G

Variant summary

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

The NM_006103.4(WFDC2):​c.224-2844C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 151,620 control chromosomes in the GnomAD database, including 9,327 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 0.32 (9327 hom., cov: 31)
• Consequence: WFDC2 NM_006103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.838

Genes affected

WFDC2 (HGNC:15939): (WAP four-disulfide core domain 2) This gene encodes a protein that is a member of the WFDC domain family. The WFDC domain, or WAP Signature motif, contains eight cysteines forming four disulfide bonds at the core of the protein, and functions as a protease inhibitor in many family members. This gene is expressed in pulmonary epithelial cells, and was also found to be expressed in some ovarian cancers. The encoded protein is a small secretory protein, which may be involved in sperm maturation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WFDC2	NM_006103.4	c.224-2844C>G		intron_variant		ENST00000372676.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WFDC2	ENST00000372676.8	c.224-2844C>G		intron_variant		1	NM_006103.4	P1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48788 AN: 151500 Hom.: 9295 Cov.: 31

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.322 AC: 48870 AN: 151620 Hom.: 9327 Cov.: 31 AF XY: 0.329 AC XY: 24380 AN XY: 74082

Gnomad4 AFR AF: 0.492

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.616

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.250

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.336

Alfa AF: 0.251 Hom.: 711

Bravo AF: 0.335

Asia WGS AF: 0.546 AC: 1898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.38

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

Other links and lift over

dbSNP: rs6073751; hg19: chr20-44105738;