rs198978

chr19-50879816-G-T

Variant summary

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

The NM_005551.5(KLK2):c.*1257G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 229,236 control chromosomes in the GnomAD database, including 21,369 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 0.44 (16249 hom., cov: 32)
  • Exomes 𝑓: 0.35 (5120 hom.)
• Consequence: KLK2 NM_005551.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLK2	NM_005551.5	c.*1257G>T		3_prime_UTR_variant	5/5	ENST00000325321.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLK2	ENST00000325321.8	c.*1257G>T		3_prime_UTR_variant	5/5	1	NM_005551.5	P1
KLK2	ENST00000358049.8	c.*1408G>T		3_prime_UTR_variant	5/5	1
KLK2	ENST00000597439.1	c.*1572G>T		3_prime_UTR_variant, NMD_transcript_variant	5/5	1
KLK2	ENST00000391810.6	c.*1257G>T		3_prime_UTR_variant	4/4	2

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66499 AN: 151954 Hom.: 16214 Cov.: 32

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.416

GnomAD4 exome AF: 0.353 AC: 27243 AN: 77164 Hom.: 5120 Cov.: 0 AF XY: 0.350 AC XY: 12399 AN XY: 35424

Gnomad4 AFR exome AF: 0.662

Gnomad4 AMR exome AF: 0.359

Gnomad4 ASJ exome AF: 0.359

Gnomad4 EAS exome AF: 0.244

Gnomad4 SAS exome AF: 0.287

Gnomad4 FIN exome AF: 0.423

Gnomad4 NFE exome AF: 0.350

Gnomad4 OTH exome AF: 0.386

GnomAD4 genome AF: 0.438 AC: 66586 AN: 152072 Hom.: 16249 Cov.: 32 AF XY: 0.431 AC XY: 32039 AN XY: 74342

Gnomad4 AFR AF: 0.671

Gnomad4 AMR AF: 0.366

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.355

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.419

Alfa AF: 0.428 Hom.: 2308

Bravo AF: 0.451

Asia WGS AF: 0.341 AC: 1190 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	0.80
Dann	Benign	0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs198978; hg19: chr19-51383072;