ENST00000596950.5:n.164G>A

Variant names:

• chr19-50873233-G-A
• rs11670728
• ENST00000596950.5:n.164G>A

Variant summary

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

The ENST00000596950.5(KLK2):​n.164G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 533,426 control chromosomes in the GnomAD database, including 32,551 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 0.29 (7881 hom., cov: 25)
  • Exomes 𝑓: 0.34 (24670 hom.)
• Consequence: KLK2 ENST00000596950.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.03
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000596950.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK2	NM_005551.5	MANE Select	c.-241G>A		upstream_gene	N/A	NP_005542.1
	KLK2	NM_001002231.3		c.-241G>A		upstream_gene	N/A	NP_001002231.1
	KLK2	NM_001256080.2		c.-387G>A		upstream_gene	N/A	NP_001243009.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK2	ENST00000596950.5	TSL:1	n.164G>A		non_coding_transcript_exon	Exon 2 of 4
	KLK2	ENST00000595375.5	TSL:4	n.200G>A		non_coding_transcript_exon	Exon 2 of 3
	KLK2	ENST00000597509.5	TSL:4	n.294G>A		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes AF: 0.294 AC: 43389 AN: 147648 Hom.: 7878 Cov.: 25

Gnomad AFR AF: 0.0932

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.273

GnomAD4 exome AF: 0.344 AC: 132836 AN: 385660 Hom.: 24670 Cov.: 0 AF XY: 0.337 AC XY: 68025 AN XY: 201946

African (AFR) AF: 0.0910 AC: 843 AN: 9268

American (AMR) AF: 0.422 AC: 6546 AN: 15528

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 3409 AN: 12326

East Asian (EAS) AF: 0.440 AC: 11459 AN: 26022

South Asian (SAS) AF: 0.190 AC: 6775 AN: 35714

European-Finnish (FIN) AF: 0.429 AC: 12387 AN: 28880

Middle Eastern (MID) AF: 0.190 AC: 345 AN: 1818

European-Non Finnish (NFE) AF: 0.359 AC: 83548 AN: 232902

Other (OTH) AF: 0.324 AC: 7524 AN: 23202

GnomAD4 genome AF: 0.294 AC: 43404 AN: 147766 Hom.: 7881 Cov.: 25 AF XY: 0.295 AC XY: 21141 AN XY: 71728

African (AFR) AF: 0.0931 AC: 3738 AN: 40156

American (AMR) AF: 0.403 AC: 5880 AN: 14578

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 973 AN: 3452

East Asian (EAS) AF: 0.432 AC: 2152 AN: 4986

South Asian (SAS) AF: 0.182 AC: 815 AN: 4472

European-Finnish (FIN) AF: 0.428 AC: 4270 AN: 9984

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

European-Non Finnish (NFE) AF: 0.368 AC: 24677 AN: 66970

Other (OTH) AF: 0.278 AC: 551 AN: 1982

Alfa AF: 0.351 Hom.: 7210

Bravo AF: 0.286

Asia WGS AF: 0.303 AC: 1053 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	17
DANN	Benign	0.23
PhyloP100		2.0
PromoterAI		-0.16	Neutral

Splicing

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

Other links and lift over

dbSNP: rs11670728; hg19: chr19-51376489;