Genetic Variant KLK2:n.*1700G>T (chr19-50879944-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000597439.1(KLK2):n.*1700G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.059 in 230,276 control chromosomes in the GnomAD database, including 515 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 0.058 ( 338 hom., cov: 32)

Exomes 𝑓: 0.061 ( 177 hom. )

Consequence

KLK2
ENST00000597439.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.738

Publications

8 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:

Genome browser will be placed here

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=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLK2	NM_005551.5 link	c.*1385G>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000325321.8	NP_005542.1	P20151-1A0A024R4J4B4DU77

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK2	ENST00000325321.8 link	c.*1385G>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_005551.5	ENSP00000313581.2		P20151-1

Frequencies

GnomAD3 genomes

AF:

0.0581

AC:

8842

AN:

152160

Hom.:

338

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0149

Gnomad AMI

AF:

0.172

Gnomad AMR

AF:

0.0496

Gnomad ASJ

AF:

0.0652

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0163

Gnomad FIN

AF:

0.0851

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0878

Gnomad OTH

AF:

0.0593

GnomAD4 exome

AF:

0.0607

AC:

4735

AN:

77998

Hom.:

177

Cov.:

AF XY:

0.0610

AC XY:

2189

AN XY:

35886

show subpopulations

African (AFR)

AF:

0.0127

AC:

AN:

3706

American (AMR)

AF:

0.0365

AC:

AN:

2414

Ashkenazi Jewish (ASJ)

AF:

0.0583

AC:

288

AN:

4936

East Asian (EAS)

AF:

0.0000905

AC:

AN:

11044

South Asian (SAS)

AF:

0.0207

AC:

AN:

676

European-Finnish (FIN)

AF:

0.107

AC:

AN:

Middle Eastern (MID)

AF:

0.0399

AC:

AN:

476

European-Non Finnish (NFE)

AF:

0.0798

AC:

3842

AN:

48130

Other (OTH)

AF:

0.0655

AC:

430

AN:

6560

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

215

431

646

862

1077

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:

0.0581

AC:

8845

AN:

152278

Hom.:

338

Cov.:

AF XY:

0.0564

AC XY:

4199

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0148

AC:

616

AN:

41566

American (AMR)

AF:

0.0496

AC:

758

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0652

AC:

226

AN:

3468

East Asian (EAS)

AF:

0.000578

AC:

AN:

5186

South Asian (SAS)

AF:

0.0168

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0851

AC:

903

AN:

10614

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0878

AC:

5970

AN:

68008

Other (OTH)

AF:

0.0587

AC:

124

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

422

843

1265

1686

2108

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

106

212

318

424

530

<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:

0.0474

Hom.:

Bravo

AF:

0.0540

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

3.2

(source)

DANN

Benign

0.69

PhyloP100

0.74

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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