Genetic Variant WFIKKN2:c.*659C>T (chr17-50841678-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_175575.6(WFIKKN2):c.*659C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 151,738 control chromosomes in the GnomAD database, including 26,077 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 0.57 ( 26067 hom., cov: 30)

Exomes 𝑓: 0.67 ( 10 hom. )

Consequence

WFIKKN2
NM_175575.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.904

Publications

7 publications found

Variant links:

Genes affected

WFIKKN2 (HGNC:30916): (WAP, follistatin/kazal, immunoglobulin, kunitz and netrin domain containing 2) The WFIKKN1 protein contains a WAP domain, follistatin domain, immunoglobulin domain, two tandem Kunitz domains, and an NTR domain. This gene encodes a WFIKKN1-related protein which has the same domain organization as the WFIKKN1 protein. The WAP-type, follistatin type, Kunitz-type, and NTR-type protease inhibitory domains may control the action of multiple types of proteases. [provided by RefSeq, Jul 2008]

WFIKKN2 links:

ENSG00000261976 (HGNC:):

ENSG00000261976 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WFIKKN2	NM_175575.6 link	c.*659C>T		3_prime_UTR_variant	Exon 2 of 2	ENST00000311378.5	NP_783165.1
WFIKKN2	NM_001330341.2 link	c.*659C>T		3_prime_UTR_variant	Exon 2 of 2		NP_001317270.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
WFIKKN2	ENST00000311378.5 link	c.*659C>T	3_prime_UTR_variant	Exon 2 of 2	1	NM_175575.6	ENSP00000311184.4
ENSG00000261976	ENST00000759459.1 link	n.323G>A	non_coding_transcript_exon_variant	Exon 4 of 4
ENSG00000261976	ENST00000759460.1 link	n.282G>A	non_coding_transcript_exon_variant	Exon 3 of 3
ENSG00000261976	ENST00000572491.2 link	n.-52G>A	upstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.573

AC:

86887

AN:

151576

Hom.:

26050

Cov.:

show subpopulations

Gnomad AFR

AF:

0.393

Gnomad AMI

AF:

0.686

Gnomad AMR

AF:

0.540

Gnomad ASJ

AF:

0.693

Gnomad EAS

AF:

0.421

Gnomad SAS

AF:

0.488

Gnomad FIN

AF:

0.654

Gnomad MID

AF:

0.659

Gnomad NFE

AF:

0.686

Gnomad OTH

AF:

0.619

GnomAD4 exome

AF:

0.667

AC:

AN:

Hom.:

Cov.:

AF XY:

0.545

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.750

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.700

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.573

AC:

86943

AN:

151696

Hom.:

26067

Cov.:

AF XY:

0.567

AC XY:

42056

AN XY:

74114

show subpopulations

African (AFR)

AF:

0.393

AC:

16233

AN:

41326

American (AMR)

AF:

0.539

AC:

8223

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.693

AC:

2402

AN:

3468

East Asian (EAS)

AF:

0.422

AC:

2164

AN:

5126

South Asian (SAS)

AF:

0.489

AC:

2350

AN:

4804

European-Finnish (FIN)

AF:

0.654

AC:

6852

AN:

10482

Middle Eastern (MID)

AF:

0.656

AC:

193

AN:

294

European-Non Finnish (NFE)

AF:

0.686

AC:

46590

AN:

67928

Other (OTH)

AF:

0.622

AC:

1310

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1770

3540

5310

7080

8850

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

734

1468

2202

2936

3670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.652

Hom.:

80636

Bravo

AF:

0.554

Asia WGS

AF:

0.507

AC:

1757

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.39

(source)

DANN

Benign

0.57

PhyloP100

-0.90

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over