20-45477098-C-G

Variant names:

• chr20-45477098-C-G
• rs6073751
• NM_006103.4:c.224-2844C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
WFDC2	NM_006103.4	c.224-2844C>G		intron_variant	Intron 2 of 3	ENST00000372676.8	NP_006094.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WFDC2	ENST00000372676.8	c.224-2844C>G		intron_variant	Intron 2 of 3	1	NM_006103.4	ENSP00000361761.3

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

African (AFR) AF: 0.492 AC: 20316 AN: 41286

American (AMR) AF: 0.359 AC: 5470 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 816 AN: 3466

East Asian (EAS) AF: 0.616 AC: 3153 AN: 5116

South Asian (SAS) AF: 0.419 AC: 2016 AN: 4806

European-Finnish (FIN) AF: 0.250 AC: 2620 AN: 10484

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13595 AN: 67902

Other (OTH) AF: 0.336 AC: 707 AN: 2104

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
PhyloP100		-0.84
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: rs6073751; hg19: chr20-44105738;