19-50870562-A-G

Variant names:

• chr19-50870562-A-G
• rs2739476
• ENST00000593493.5:c.-332-2621A>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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK2	ENST00000593493.5	c.-332-2621A>G		intron_variant	Intron 1 of 3	3		ENSP00000472852.1
KLK2	ENST00000596950.5	n.-183A>G		upstream_gene_variant		1
KLK2	ENST00000595375.5	n.-39A>G		upstream_gene_variant		4
KLK2	ENST00000597509.5	n.-53A>G		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;