19-50869139-C-T

Variant names:

• chr19-50869139-C-T
• rs2569739
• ENST00000593493.5:c.-332-4044C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000593493.5(KLK2):​c.-332-4044C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 151,904 control chromosomes in the GnomAD database, including 22,141 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 0.53 (22141 hom., cov: 31)
• Consequence: KLK2 ENST00000593493.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.578
• Publications: 5 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK2	ENST00000593493.5	c.-332-4044C>T		intron_variant	Intron 1 of 3	3		ENSP00000472852.1

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81210 AN: 151786 Hom.: 22128 Cov.: 31

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.521

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.535 AC: 81259 AN: 151904 Hom.: 22141 Cov.: 31 AF XY: 0.536 AC XY: 39812 AN XY: 74256

African (AFR) AF: 0.455 AC: 18826 AN: 41404

American (AMR) AF: 0.573 AC: 8750 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 1945 AN: 3470

East Asian (EAS) AF: 0.784 AC: 4054 AN: 5174

South Asian (SAS) AF: 0.565 AC: 2714 AN: 4806

European-Finnish (FIN) AF: 0.578 AC: 6103 AN: 10550

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.547 AC: 37158 AN: 67924

Other (OTH) AF: 0.527 AC: 1110 AN: 2106

Alfa AF: 0.541 Hom.: 18574

Bravo AF: 0.530

Asia WGS AF: 0.699 AC: 2430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.82
DANN	Benign	0.63
PhyloP100		-0.58

Splicing

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

Other links and lift over

dbSNP: rs2569739; hg19: chr19-51372395;