rs3760728

Positions:

• chr19-50871336-C-G
• chr19-50871336-C-T

Variant summary

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

The ENST00000593493.5(KLK2):​c.-332-1847C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 151,944 control chromosomes in the GnomAD database, including 8,190 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 0.30 (8190 hom., cov: 32)
• Consequence: KLK2 ENST00000593493.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.42

Genes affected

KLK2 (HGNC:):

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.50871336C>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK2	ENST00000596950.5	n.113+479C>G		intron_variant		1
KLK2	ENST00000593493.5	c.-332-1847C>G		intron_variant		3		ENSP00000472852.1
KLK2	ENST00000595375.5	n.149+587C>G		intron_variant		4
KLK2	ENST00000597509.5	n.243+479C>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45542 AN: 151826 Hom.: 8187 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.300 AC: 45558 AN: 151944 Hom.: 8190 Cov.: 32 AF XY: 0.302 AC XY: 22420 AN XY: 74242

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.275

Gnomad4 EAS AF: 0.435

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.368

Gnomad4 OTH AF: 0.283

Alfa AF: 0.229 Hom.: 625

Bravo AF: 0.291

Asia WGS AF: 0.303 AC: 1055 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
DANN	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3760728; hg19: chr19-51374592; COSMIC: COSV57571011;