ENST00000593493.5:c.-333+2509T>C

Variant names:

• chr19-50864188-T-C
• rs62113226
• ENST00000593493.5:c.-333+2509T>C

Variant summary

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

The ENST00000593493.5(KLK2):​c.-333+2509T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.062 in 152,158 control chromosomes in the GnomAD database, including 329 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 0.062 (329 hom., cov: 32)
• Consequence: KLK2 ENST00000593493.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.106

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.134 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.-333+2509T>C		intron_variant	Intron 1 of 3	3		ENSP00000472852.1

Frequencies

GnomAD3 genomes AF: 0.0621 AC: 9442 AN: 152040 Hom.: 330 Cov.: 32

Gnomad AFR AF: 0.0445

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0559

Gnomad ASJ AF: 0.0818

Gnomad EAS AF: 0.0141

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.0422

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0745

Gnomad OTH AF: 0.0684

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

GnomAD4 genome AF: 0.0620 AC: 9437 AN: 152158 Hom.: 329 Cov.: 32 AF XY: 0.0615 AC XY: 4577 AN XY: 74396

Gnomad4 AFR AF: 0.0445

Gnomad4 AMR AF: 0.0557

Gnomad4 ASJ AF: 0.0818

Gnomad4 EAS AF: 0.0141

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.0422

Gnomad4 NFE AF: 0.0745

Gnomad4 OTH AF: 0.0676

Alfa AF: 0.0707 Hom.: 81

Bravo AF: 0.0602

Asia WGS AF: 0.0810 AC: 282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.4
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs62113226; hg19: chr19-51367444;