chr19-50865864-T-A

Variant names:

• chr19-50865864-T-A
• rs2739460
• ENST00000593493.5:c.-333+4185T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000593493.5(KLK2):​c.-333+4185T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 152,148 control chromosomes in the GnomAD database, including 15,597 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 0.43 (15597 hom., cov: 32)
• Consequence: KLK2 ENST00000593493.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.106
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 = 0.698 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000593493.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK2	ENST00000593493.5	TSL:3	c.-333+4185T>A		intron	N/A	ENSP00000472852.1

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64821 AN: 152030 Hom.: 15588 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.428

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.426 AC: 64845 AN: 152148 Hom.: 15597 Cov.: 32 AF XY: 0.431 AC XY: 32068 AN XY: 74386

African (AFR) AF: 0.200 AC: 8313 AN: 41520

American (AMR) AF: 0.507 AC: 7750 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1540 AN: 3470

East Asian (EAS) AF: 0.717 AC: 3706 AN: 5170

South Asian (SAS) AF: 0.523 AC: 2522 AN: 4824

European-Finnish (FIN) AF: 0.552 AC: 5850 AN: 10594

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.497 AC: 33778 AN: 67980

Other (OTH) AF: 0.435 AC: 917 AN: 2110

Alfa AF: 0.449 Hom.: 1978

Bravo AF: 0.410

Asia WGS AF: 0.625 AC: 2173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.7
DANN	Benign	0.63
PhyloP100		0.11

Splicing

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

Other links and lift over

dbSNP: rs2739460; hg19: chr19-51369120;