Genetic Variant ENST00000593493.5: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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000593493.5. 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

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
KLK2	ENST00000593493.5	TSL:3	c.-332-2621A>G	intron	N/A	ENSP00000472852.1
KLK2	ENST00000596950.5	TSL:1	n.-183A>G	upstream_gene	N/A
KLK2	ENST00000595375.5	TSL:4	n.-39A>G	upstream_gene	N/A

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over