19-50870562-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.08

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLK2	ENST00000593493.5	c.-332-2621A>G		intron_variant		3
KLK2	ENST00000595375.5			upstream_gene_variant		4

Frequencies

GnomAD3 genomes AF: 0.540 AC: 82148 AN: 152044 Hom.: 22566 Cov.: 33

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: 65 AN: 108 Hom.: 18 Cov.: 0 AF XY: 0.579 AC XY: 44 AN XY: 76

Gnomad4 AFR exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.667

Gnomad4 NFE exome AF: 0.614

Gnomad4 OTH exome AF: 0.625

GnomAD4 genome AF: 0.540 AC: 82198 AN: 152162 Hom.: 22581 Cov.: 33 AF XY: 0.541 AC XY: 40250 AN XY: 74396

Gnomad4 AFR AF: 0.472

Gnomad4 AMR AF: 0.576

Gnomad4 ASJ AF: 0.561

Gnomad4 EAS AF: 0.785

Gnomad4 SAS AF: 0.565

Gnomad4 FIN AF: 0.578

Gnomad4 NFE AF: 0.548

Gnomad4 OTH AF: 0.534

Alfa AF: 0.514 Hom.: 4721

Bravo AF: 0.536

Asia WGS AF: 0.702 AC: 2441 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.030
Dann	Benign	0.22

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2739476; hg19: chr19-51373818;