rs198978

Variant names:

• chr19-50879816-G-T
• rs198978
• NM_005551.5:c.*1257G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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 (AFR) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005551.5. 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
	KLK2	NM_005551.5	MANE Select	c.*1257G>T		3_prime_UTR	Exon 5 of 5	NP_005542.1
	KLK2	NM_001002231.3		c.*1408G>T		3_prime_UTR	Exon 5 of 5	NP_001002231.1
	KLK2	NM_001256080.2		c.*1257G>T		3_prime_UTR	Exon 4 of 4	NP_001243009.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK2	ENST00000325321.8	TSL:1 MANE Select	c.*1257G>T		3_prime_UTR	Exon 5 of 5	ENSP00000313581.2
	KLK2	ENST00000358049.8	TSL:1	c.*1408G>T		3_prime_UTR	Exon 5 of 5	ENSP00000350748.3
	KLK2	ENST00000597439.1	TSL:1	n.*1572G>T		non_coding_transcript_exon	Exon 5 of 5	ENSP00000471214.1

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

African (AFR) AF: 0.662 AC: 2438 AN: 3682

American (AMR) AF: 0.359 AC: 852 AN: 2372

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1751 AN: 4874

East Asian (EAS) AF: 0.244 AC: 2683 AN: 10990

South Asian (SAS) AF: 0.287 AC: 194 AN: 676

European-Finnish (FIN) AF: 0.423 AC: 22 AN: 52

Middle Eastern (MID) AF: 0.355 AC: 167 AN: 470

European-Non Finnish (NFE) AF: 0.350 AC: 16642 AN: 47586

Other (OTH) AF: 0.386 AC: 2494 AN: 6462

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

African (AFR) AF: 0.671 AC: 27823 AN: 41458

American (AMR) AF: 0.366 AC: 5603 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1267 AN: 3470

East Asian (EAS) AF: 0.217 AC: 1120 AN: 5170

South Asian (SAS) AF: 0.319 AC: 1539 AN: 4830

European-Finnish (FIN) AF: 0.355 AC: 3752 AN: 10570

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.355 AC: 24148 AN: 67962

Other (OTH) AF: 0.419 AC: 884 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.80
DANN	Benign	0.31
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs198978; hg19: chr19-51383072;