rs11670728

Positions:

• chr19-50873233-G-A

Variant summary

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

The ENST00000593493.5(KLK2):​c.-282G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 533,426 control chromosomes in the GnomAD database, including 32,551 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 0.29 (7881 hom., cov: 25)
  • Exomes 𝑓: 0.34 (24670 hom.)
• Consequence: KLK2 ENST00000593493.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.03

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK2	ENST00000596950.5	n.164G>A		non_coding_transcript_exon_variant	2/4	1
KLK2	ENST00000593493.5	c.-282G>A		5_prime_UTR_variant	2/4	3		ENSP00000472852
KLK2	ENST00000595375.5	n.200G>A		non_coding_transcript_exon_variant	2/3	4
KLK2	ENST00000597509.5	n.294G>A		non_coding_transcript_exon_variant	2/4	4

Frequencies

GnomAD3 genomes AF: 0.294 AC: 43389 AN: 147648 Hom.: 7878 Cov.: 25

Gnomad AFR AF: 0.0932

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.273

GnomAD4 exome AF: 0.344 AC: 132836 AN: 385660 Hom.: 24670 Cov.: 0 AF XY: 0.337 AC XY: 68025 AN XY: 201946

Gnomad4 AFR exome AF: 0.0910

Gnomad4 AMR exome AF: 0.422

Gnomad4 ASJ exome AF: 0.277

Gnomad4 EAS exome AF: 0.440

Gnomad4 SAS exome AF: 0.190

Gnomad4 FIN exome AF: 0.429

Gnomad4 NFE exome AF: 0.359

Gnomad4 OTH exome AF: 0.324

GnomAD4 genome AF: 0.294 AC: 43404 AN: 147766 Hom.: 7881 Cov.: 25 AF XY: 0.295 AC XY: 21141 AN XY: 71728

Gnomad4 AFR AF: 0.0931

Gnomad4 AMR AF: 0.403

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.368

Gnomad4 OTH AF: 0.278

Alfa AF: 0.356 Hom.: 3744

Bravo AF: 0.286

Asia WGS AF: 0.303 AC: 1053 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	17
DANN	Benign	0.23

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11670728; hg19: chr19-51376489;