rs62113216

Variant names:

• chr19-50861547-T-A
• rs62113216
• ENST00000593493.5:c.-465T>A

Variant summary

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

The ENST00000593493.5(KLK2):​c.-465T>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,236 control chromosomes in the GnomAD database, including 1,347 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 0.12 (1347 hom., cov: 32)
  • Exomes 𝑓: 0.065 (0 hom.)
• Consequence: KLK2 ENST00000593493.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.241

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.195 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.-465T>A		upstream_gene_variant		3		ENSP00000472852.1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18054 AN: 152056 Hom.: 1348 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.0764

Gnomad ASJ AF: 0.0988

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0561

Gnomad FIN AF: 0.0977

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0963

Gnomad OTH AF: 0.111

GnomAD4 exome AF: 0.0645 AC: 4 AN: 62 Hom.: 0 Cov.: 0 AF XY: 0.0870 AC XY: 4 AN XY: 46

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.0588

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.119 AC: 18073 AN: 152174 Hom.: 1347 Cov.: 32 AF XY: 0.117 AC XY: 8669 AN XY: 74400

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.0763

Gnomad4 ASJ AF: 0.0988

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0562

Gnomad4 FIN AF: 0.0977

Gnomad4 NFE AF: 0.0963

Gnomad4 OTH AF: 0.110

Alfa AF: 0.107 Hom.: 132

Bravo AF: 0.124

Asia WGS AF: 0.0290 AC: 101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs62113216; hg19: chr19-51364803;