rs11084039

Positions:

• chr19-50872963-G-A
• chr19-50872963-G-T

Variant summary

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

The ENST00000596950.5(KLK2):​n.114-220G>A variant causes a intron, non coding transcript 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, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.597

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=-0.96).
• 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/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK2	ENST00000596950.5	n.114-220G>A		intron_variant, non_coding_transcript_variant		1
KLK2	ENST00000593493.5	c.-332-220G>A		intron_variant		3		ENSP00000472852
KLK2	ENST00000595375.5	n.150-220G>A		intron_variant, non_coding_transcript_variant		4
KLK2	ENST00000597509.5	n.244-220G>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.0943

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.434

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.434

Gnomad4 NFE AF: 0.370

Gnomad4 OTH AF: 0.285

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11084039; hg19: chr19-51376219;