rs62113216

chr19-50861547-T-A

Variant summary

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

The 19-50861547-T-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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLK2	ENST00000593493.5			upstream_gene_variant		3

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;