Variant 19-50876637-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_005551.5(KLK2):c.372C>T(p.Leu124Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 1,613,856 control chromosomes in the GnomAD database, including 96,744 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 0.41 ( 13742 hom., cov: 32)

Exomes 𝑓: 0.33 ( 83002 hom. )

Consequence

KLK2
NM_005551.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.29

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:

KLK2 (HGNC:):

KLK2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP7

Synonymous conserved (PhyloP=-2.29 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLK2	NM_005551.5 linkuse as main transcript	c.372C>T	p.Leu124Leu	synonymous_variant	3/5	ENST00000325321.8	NP_005542.1	P20151-1A0A024R4J4B4DU77

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK2	ENST00000325321.8 linkuse as main transcript	c.372C>T	p.Leu124Leu	synonymous_variant	3/5	1	NM_005551.5	ENSP00000313581.2		P20151-1

Frequencies

GnomAD3 genomes

AF:

0.405

AC:

61564

AN:

151948

Hom.:

13725

Cov.:

show subpopulations

Gnomad AFR

AF:

0.605

Gnomad AMI

AF:

0.339

Gnomad AMR

AF:

0.325

Gnomad ASJ

AF:

0.368

Gnomad EAS

AF:

0.304

Gnomad SAS

AF:

0.444

Gnomad FIN

AF:

0.380

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.315

Gnomad OTH

AF:

0.375

GnomAD3 exomes

AF:

0.349

AC:

87781

AN:

251234

Hom.:

16291

AF XY:

0.350

AC XY:

47500

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.613

Gnomad AMR exome

AF:

0.271

Gnomad ASJ exome

AF:

0.372

Gnomad EAS exome

AF:

0.305

Gnomad SAS exome

AF:

0.423

Gnomad FIN exome

AF:

0.381

Gnomad NFE exome

AF:

0.315

Gnomad OTH exome

AF:

0.337

GnomAD4 exome

AF:

0.332

AC:

485629

AN:

1461790

Hom.:

83002

Cov.:

AF XY:

0.334

AC XY:

242952

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.617

Gnomad4 AMR exome

AF:

0.281

Gnomad4 ASJ exome

AF:

0.376

Gnomad4 EAS exome

AF:

0.338

Gnomad4 SAS exome

AF:

0.422

Gnomad4 FIN exome

AF:

0.377

Gnomad4 NFE exome

AF:

0.315

Gnomad4 OTH exome

AF:

0.346

GnomAD4 genome

AF:

0.405

AC:

61626

AN:

152066

Hom.:

13742

Cov.:

AF XY:

0.405

AC XY:

30115

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.605

Gnomad4 AMR

AF:

0.324

Gnomad4 ASJ

AF:

0.368

Gnomad4 EAS

AF:

0.304

Gnomad4 SAS

AF:

0.443

Gnomad4 FIN

AF:

0.380

Gnomad4 NFE

AF:

0.315

Gnomad4 OTH

AF:

0.380

Alfa

AF:

0.339

Hom.:

15108

Bravo

AF:

0.409

Asia WGS

AF:

0.434

AC:

1511

AN:

3478

EpiCase

AF:

0.320

EpiControl

AF:

0.315

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.52

DANN

Benign

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over