rs62113226

chr19-50864188-T-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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLK2	ENST00000593493.5	c.-333+2509T>C		intron_variant		3

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;