Genetic Variant KLK2:c.-332-2621A>G (chr19-50870562-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000593493.5(KLK2):c.-332-2621A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 152,270 control chromosomes in the GnomAD database, including 22,599 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 0.54 ( 22581 hom., cov: 33)

Exomes 𝑓: 0.60 ( 18 hom. )

Consequence

KLK2
ENST00000593493.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.08

Publications

7 publications found

Variant links:

Genes affected

KLK2 (HGNC:6363): (kallikrein related peptidase 2) This gene encodes a member of the grandular kallikrein protein family. Kallikreins are a subgroup of serine proteases that are clustered on chromosome 19. Members of this family are involved in a diverse array of biological functions. The protein encoded by this gene is a highly active trypsin-like serine protease that selectively cleaves at arginine residues. This protein is primarily expressed in prostatic tissue and is responsible for cleaving pro-prostate-specific antigen into its enzymatically active form. This gene is highly expressed in prostate tumor cells and may be a prognostic maker for prostate cancer risk. Alternate splicing results in both coding and non-coding transcript variants. [provided by RefSeq, Jan 2012]

KLK2 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=-1.01).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
KLK2	ENST00000593493.5 link	c.-332-2621A>G	intron_variant	Intron 1 of 3	3	ENSP00000472852.1
KLK2	ENST00000596950.5 link	n.-183A>G	upstream_gene_variant		1
KLK2	ENST00000595375.5 link	n.-39A>G	upstream_gene_variant		4
KLK2	ENST00000597509.5 link	n.-53A>G	upstream_gene_variant		4

Frequencies

GnomAD3 genomes

AF:

0.540

AC:

82148

AN:

152044

Hom.:

22566

Cov.:

show subpopulations

Gnomad AFR

AF:

0.472

Gnomad AMI

AF:

0.515

Gnomad AMR

AF:

0.576

Gnomad ASJ

AF:

0.561

Gnomad EAS

AF:

0.785

Gnomad SAS

AF:

0.565

Gnomad FIN

AF:

0.578

Gnomad MID

AF:

0.459

Gnomad NFE

AF:

0.548

Gnomad OTH

AF:

0.528

GnomAD4 exome

AF:

0.602

AC:

AN:

108

Hom.:

Cov.:

AF XY:

0.579

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.667

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.614

AC:

AN:

Other (OTH)

AF:

0.625

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

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:

0.540

AC:

82198

AN:

152162

Hom.:

22581

Cov.:

AF XY:

0.541

AC XY:

40250

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.472

AC:

19599

AN:

41538

American (AMR)

AF:

0.576

AC:

8810

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.561

AC:

1944

AN:

3468

East Asian (EAS)

AF:

0.785

AC:

4050

AN:

5162

South Asian (SAS)

AF:

0.565

AC:

2722

AN:

4820

European-Finnish (FIN)

AF:

0.578

AC:

6121

AN:

10594

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.548

AC:

37220

AN:

67960

Other (OTH)

AF:

0.534

AC:

1131

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

2017

4033

6050

8066

10083

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

726

1452

2178

2904

3630

<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:

0.526

Hom.:

9846

Bravo

AF:

0.536

Asia WGS

AF:

0.702

AC:

2441

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

0.030

(source)

DANN

Benign

0.22

PhyloP100

-3.1

Splicing

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