19-50876637-C-T

Variant names:

• chr19-50876637-C-T
• rs198972
• NM_005551.5:c.372C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005551.5(KLK2):​c.372C>T​(p.Leu124Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 1,613,856 control chromosomes in the GnomAD database, including 96,744 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 0.41 (13742 hom., cov: 32)
  • Exomes 𝑓: 0.33 (83002 hom.)
• Consequence: KLK2 NM_005551.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29
• Publications: 31 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=-2.29 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.598 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.372C>T	p.Leu124Leu	synonymous	Exon 3 of 5	NP_005542.1	P20151-1
	KLK2	NM_001002231.3		c.372C>T	p.Leu124Leu	synonymous	Exon 3 of 5	NP_001002231.1	P20151-2
	KLK2	NM_001256080.2		c.66C>T	p.Leu22Leu	synonymous	Exon 2 of 4	NP_001243009.1	P20151-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK2	ENST00000325321.8	TSL:1 MANE Select	c.372C>T	p.Leu124Leu	synonymous	Exon 3 of 5	ENSP00000313581.2	P20151-1
	KLK2	ENST00000358049.8	TSL:1	c.372C>T	p.Leu124Leu	synonymous	Exon 3 of 5	ENSP00000350748.3	P20151-2
	KLK2	ENST00000595316.5	TSL:1	n.*62C>T		non_coding_transcript_exon	Exon 2 of 3	ENSP00000469770.1	Q6T774

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61564 AN: 151948 Hom.: 13725 Cov.: 32

Gnomad AFR AF: 0.605

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.375

GnomAD2 exomes AF: 0.349 AC: 87781 AN: 251234 AF XY: 0.350

Gnomad AFR exome AF: 0.613

Gnomad AMR exome AF: 0.271

Gnomad ASJ exome AF: 0.372

Gnomad EAS exome AF: 0.305

Gnomad FIN exome AF: 0.381

Gnomad NFE exome AF: 0.315

Gnomad OTH exome AF: 0.337

GnomAD4 exome AF: 0.332 AC: 485629 AN: 1461790 Hom.: 83002 Cov.: 48 AF XY: 0.334 AC XY: 242952 AN XY: 727198

African (AFR) AF: 0.617 AC: 20649 AN: 33480

American (AMR) AF: 0.281 AC: 12568 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 9824 AN: 26136

East Asian (EAS) AF: 0.338 AC: 13426 AN: 39700

South Asian (SAS) AF: 0.422 AC: 36402 AN: 86258

European-Finnish (FIN) AF: 0.377 AC: 20143 AN: 53394

Middle Eastern (MID) AF: 0.325 AC: 1876 AN: 5768

European-Non Finnish (NFE) AF: 0.315 AC: 349847 AN: 1111942

Other (OTH) AF: 0.346 AC: 20894 AN: 60396

GnomAD4 genome AF: 0.405 AC: 61626 AN: 152066 Hom.: 13742 Cov.: 32 AF XY: 0.405 AC XY: 30115 AN XY: 74326

African (AFR) AF: 0.605 AC: 25070 AN: 41472

American (AMR) AF: 0.324 AC: 4956 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1278 AN: 3470

East Asian (EAS) AF: 0.304 AC: 1568 AN: 5154

South Asian (SAS) AF: 0.443 AC: 2135 AN: 4814

European-Finnish (FIN) AF: 0.380 AC: 4023 AN: 10574

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.315 AC: 21390 AN: 67978

Other (OTH) AF: 0.380 AC: 801 AN: 2110

Alfa AF: 0.346 Hom.: 20961

Bravo AF: 0.409

Asia WGS AF: 0.434 AC: 1511 AN: 3478

EpiCase AF: 0.320

EpiControl AF: 0.315

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.52
DANN	Benign	0.48
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs198972; hg19: chr19-51379893; COSMIC: COSV57568989; COSMIC: COSV57568989;