19-50871336-C-G

Variant names:

• chr19-50871336-C-G
• rs3760728
• ENST00000596950.5:n.113+479C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000593493.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK2	ENST00000596950.5	TSL:1	n.113+479C>G		intron	N/A
	KLK2	ENST00000593493.5	TSL:3	c.-332-1847C>G		intron	N/A	ENSP00000472852.1	M0R2W5
	KLK2	ENST00000595375.5	TSL:4	n.149+587C>G		intron	N/A

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

African (AFR) AF: 0.113 AC: 4694 AN: 41432

American (AMR) AF: 0.407 AC: 6205 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 954 AN: 3470

East Asian (EAS) AF: 0.435 AC: 2251 AN: 5170

South Asian (SAS) AF: 0.190 AC: 909 AN: 4796

European-Finnish (FIN) AF: 0.432 AC: 4555 AN: 10546

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

European-Non Finnish (NFE) AF: 0.368 AC: 25034 AN: 67952

Other (OTH) AF: 0.283 AC: 597 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
DANN	Benign	0.52
PhyloP100		-4.4

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3760728;

hg19: chr19-51374592;

COSMIC: COSV57571011;