19-50861367-A-G

Variant names:

• chr19-50861367-A-G
• rs2735839
• ENST00000593493.5:c.-645A>G

Variant summary

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

The ENST00000593493.5(KLK2):​c.-645A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 152,054 control chromosomes in the GnomAD database, including 47,252 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 0.78 (47252 hom., cov: 31)
• Consequence: KLK2 ENST00000593493.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.238
• Publications: 205 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=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.852 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.-645A>G		upstream_gene_variant		3		ENSP00000472852.1

Frequencies

GnomAD3 genomes AF: 0.782 AC: 118866 AN: 151936 Hom.: 47228 Cov.: 31

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.812

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.876

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.857

Gnomad OTH AF: 0.777

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

GnomAD4 genome AF: 0.782 AC: 118941 AN: 152054 Hom.: 47252 Cov.: 31 AF XY: 0.779 AC XY: 57874 AN XY: 74308

African (AFR) AF: 0.676 AC: 27988 AN: 41430

American (AMR) AF: 0.769 AC: 11756 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.812 AC: 2820 AN: 3472

East Asian (EAS) AF: 0.585 AC: 3011 AN: 5148

South Asian (SAS) AF: 0.671 AC: 3229 AN: 4814

European-Finnish (FIN) AF: 0.876 AC: 9276 AN: 10584

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.857 AC: 58297 AN: 67996

Other (OTH) AF: 0.777 AC: 1642 AN: 2112

Alfa AF: 0.824 Hom.: 245065

Bravo AF: 0.768

Asia WGS AF: 0.620 AC: 2157 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	0.49
DANN	Benign	0.32
PhyloP100		-0.24
PromoterAI		-0.018	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2735839; hg19: chr19-51364623;