chr19-50869139-C-T

Position:

• chr19-50869139-C-T

Variant summary

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

The ENST00000593493.5(KLK2):​c.-332-4044C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 151,904 control chromosomes in the GnomAD database, including 22,141 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 0.53 (22141 hom., cov: 31)
• Consequence: KLK2 ENST00000593493.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.578

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.763 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	ENST00000593493.5	c.-332-4044C>T		intron_variant		3		ENSP00000472852

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81210 AN: 151786 Hom.: 22128 Cov.: 31

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.535 AC: 81259 AN: 151904 Hom.: 22141 Cov.: 31 AF XY: 0.536 AC XY: 39812 AN XY: 74256

Gnomad4 AFR AF: 0.455

Gnomad4 AMR AF: 0.573

Gnomad4 ASJ AF: 0.561

Gnomad4 EAS AF: 0.784

Gnomad4 SAS AF: 0.565

Gnomad4 FIN AF: 0.578

Gnomad4 NFE AF: 0.547

Gnomad4 OTH AF: 0.527

Alfa AF: 0.540 Hom.: 12920

Bravo AF: 0.530

Asia WGS AF: 0.699 AC: 2430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.82
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2569739; hg19: chr19-51372395;