dbSNP rs11670728: KLK2:n.164G>A (chr19-50873233-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000596950.5(KLK2):n.164G>A 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 0.33 in 533,426 control chromosomes in the GnomAD database, including 32,551 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 0.29 ( 7881 hom., cov: 25)

Exomes 𝑓: 0.34 ( 24670 hom. )

Consequence

KLK2
ENST00000596950.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.03

Publications

10 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=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLK2	NM_005551.5 link	c.-241G>A		upstream_gene_variant		ENST00000325321.8	NP_005542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK2	ENST00000325321.8 link	c.-241G>A		upstream_gene_variant		1	NM_005551.5	ENSP00000313581.2

Frequencies

GnomAD3 genomes

AF:

0.294

AC:

43389

AN:

147648

Hom.:

7878

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0932

Gnomad AMI

AF:

0.314

Gnomad AMR

AF:

0.403

Gnomad ASJ

AF:

0.282

Gnomad EAS

AF:

0.432

Gnomad SAS

AF:

0.183

Gnomad FIN

AF:

0.428

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.368

Gnomad OTH

AF:

0.273

GnomAD4 exome

AF:

0.344

AC:

132836

AN:

385660

Hom.:

24670

Cov.:

AF XY:

0.337

AC XY:

68025

AN XY:

201946

show subpopulations

African (AFR)

AF:

0.0910

AC:

843

AN:

9268

American (AMR)

AF:

0.422

AC:

6546

AN:

15528

Ashkenazi Jewish (ASJ)

AF:

0.277

AC:

3409

AN:

12326

East Asian (EAS)

AF:

0.440

AC:

11459

AN:

26022

South Asian (SAS)

AF:

0.190

AC:

6775

AN:

35714

European-Finnish (FIN)

AF:

0.429

AC:

12387

AN:

28880

Middle Eastern (MID)

AF:

0.190

AC:

345

AN:

1818

European-Non Finnish (NFE)

AF:

0.359

AC:

83548

AN:

232902

Other (OTH)

AF:

0.324

AC:

7524

AN:

23202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

3903

7805

11708

15610

19513

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

404

808

1212

1616

2020

<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:

0.294

AC:

43404

AN:

147766

Hom.:

7881

Cov.:

AF XY:

0.295

AC XY:

21141

AN XY:

71728

show subpopulations

African (AFR)

AF:

0.0931

AC:

3738

AN:

40156

American (AMR)

AF:

0.403

AC:

5880

AN:

14578

Ashkenazi Jewish (ASJ)

AF:

0.282

AC:

973

AN:

3452

East Asian (EAS)

AF:

0.432

AC:

2152

AN:

4986

South Asian (SAS)

AF:

0.182

AC:

815

AN:

4472

European-Finnish (FIN)

AF:

0.428

AC:

4270

AN:

9984

Middle Eastern (MID)

AF:

0.231

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.368

AC:

24677

AN:

66970

Other (OTH)

AF:

0.278

AC:

551

AN:

1982

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1242

2483

3725

4966

6208

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

428

856

1284

1712

2140

<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:

0.351

Hom.:

7210

Bravo

AF:

0.286

Asia WGS

AF:

0.303

AC:

1053

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

(source)

DANN

Benign

0.23

PhyloP100

2.0

PromoterAI

-0.16

Neutral

(source)

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