19-50872963-G-A

Variant names:

• chr19-50872963-G-A
• rs11084039
• ENST00000596950.5:n.114-220G>A

Variant summary

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

The ENST00000596950.5(KLK2):​n.114-220G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 151,914 control chromosomes in the GnomAD database, including 8,163 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 (8163 hom., cov: 29)
• Consequence: KLK2 ENST00000596950.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.597
• Publications: 4 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.419 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	ENST00000596950.5	n.114-220G>A		intron_variant	Intron 1 of 3	1
KLK2	ENST00000593493.5	c.-332-220G>A		intron_variant	Intron 1 of 3	3		ENSP00000472852.1
KLK2	ENST00000595375.5	n.150-220G>A		intron_variant	Intron 1 of 2	4
KLK2	ENST00000597509.5	n.244-220G>A		intron_variant	Intron 1 of 3	4

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44848 AN: 151794 Hom.: 8159 Cov.: 29

Gnomad AFR AF: 0.0945

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.295 AC: 44865 AN: 151914 Hom.: 8163 Cov.: 29 AF XY: 0.297 AC XY: 22082 AN XY: 74236

African (AFR) AF: 0.0943 AC: 3914 AN: 41484

American (AMR) AF: 0.406 AC: 6196 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 978 AN: 3466

East Asian (EAS) AF: 0.434 AC: 2234 AN: 5152

South Asian (SAS) AF: 0.188 AC: 900 AN: 4794

European-Finnish (FIN) AF: 0.434 AC: 4570 AN: 10538

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.370 AC: 25116 AN: 67912

Other (OTH) AF: 0.285 AC: 599 AN: 2104

Alfa AF: 0.334 Hom.: 1177

Bravo AF: 0.286

Asia WGS AF: 0.302 AC: 1050 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.1
DANN	Benign	0.41
PhyloP100		0.60
PromoterAI		0.0030	Neutral

Splicing

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

Other links and lift over

dbSNP: rs11084039; hg19: chr19-51376219;