rs198977

Variant names:

• chr19-50878521-C-T
• rs198977
• NM_005551.5:c.748C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005551.5(KLK2):​c.748C>T​(p.Arg250Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 1,613,356 control chromosomes in the GnomAD database, including 51,656 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (7272 hom., cov: 32)
  • Exomes 𝑓: 0.24 (44384 hom.)
• Consequence: KLK2 NM_005551.5 missense
• Clinical Significance: Benign criteria provided, single submitter P:1 B:1
• Conservation: PhyloP100: -7.28
• Publications: 56 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.9420853E-4).
• BP6: Variant 19-50878521-C-T is Benign according to our data. Variant chr19-50878521-C-T is described in ClinVar as Benign. ClinVar VariationId is 2573115.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.418 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.748C>T	p.Arg250Trp	missense	Exon 5 of 5	NP_005542.1	P20151-1
	KLK2	NM_001256080.2		c.442C>T	p.Arg148Trp	missense	Exon 4 of 4	NP_001243009.1	P20151-4
	KLK2	NM_001002231.3		c.*113C>T		3_prime_UTR	Exon 5 of 5	NP_001002231.1	P20151-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK2	ENST00000325321.8	TSL:1 MANE Select	c.748C>T	p.Arg250Trp	missense	Exon 5 of 5	ENSP00000313581.2	P20151-1
	KLK2	ENST00000358049.8	TSL:1	c.*113C>T		3_prime_UTR	Exon 5 of 5	ENSP00000350748.3	P20151-2
	KLK2	ENST00000597439.1	TSL:1	n.*277C>T		non_coding_transcript_exon	Exon 5 of 5	ENSP00000471214.1	P20151-3

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45087 AN: 151848 Hom.: 7255 Cov.: 32

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.306

GnomAD2 exomes AF: 0.244 AC: 61217 AN: 251292 AF XY: 0.239

Gnomad AFR exome AF: 0.429

Gnomad AMR exome AF: 0.188

Gnomad ASJ exome AF: 0.258

Gnomad EAS exome AF: 0.188

Gnomad FIN exome AF: 0.323

Gnomad NFE exome AF: 0.250

Gnomad OTH exome AF: 0.257

GnomAD4 exome AF: 0.243 AC: 354835 AN: 1461390 Hom.: 44384 Cov.: 33 AF XY: 0.240 AC XY: 174451 AN XY: 727032

African (AFR) AF: 0.422 AC: 14125 AN: 33470

American (AMR) AF: 0.195 AC: 8738 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 6784 AN: 26108

East Asian (EAS) AF: 0.220 AC: 8726 AN: 39688

South Asian (SAS) AF: 0.153 AC: 13177 AN: 86238

European-Finnish (FIN) AF: 0.319 AC: 17065 AN: 53412

Middle Eastern (MID) AF: 0.269 AC: 1549 AN: 5764

European-Non Finnish (NFE) AF: 0.242 AC: 269210 AN: 1111620

Other (OTH) AF: 0.256 AC: 15461 AN: 60372

GnomAD4 genome AF: 0.297 AC: 45135 AN: 151966 Hom.: 7272 Cov.: 32 AF XY: 0.295 AC XY: 21910 AN XY: 74264

African (AFR) AF: 0.424 AC: 17540 AN: 41416

American (AMR) AF: 0.249 AC: 3804 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 900 AN: 3470

East Asian (EAS) AF: 0.190 AC: 984 AN: 5176

South Asian (SAS) AF: 0.156 AC: 753 AN: 4814

European-Finnish (FIN) AF: 0.314 AC: 3314 AN: 10556

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16892 AN: 67942

Other (OTH) AF: 0.307 AC: 647 AN: 2108

Alfa AF: 0.259 Hom.: 17283

Bravo AF: 0.301

TwinsUK AF: 0.231 AC: 856

ALSPAC AF: 0.228 AC: 880

ESP6500AA AF: 0.426 AC: 1879

ESP6500EA AF: 0.247 AC: 2124

ExAC AF: 0.247 AC: 29972

Asia WGS AF: 0.213 AC: 745 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	1	Acute myeloid leukemia (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	1.1
DANN	Benign	0.63
DEOGEN2	Benign	0.35	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.039	T
MetaRNN	Benign	0.00029	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		-7.3
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.37
Sift	Benign	0.16	T
Sift4G	Benign	0.21	T
Polyphen		0.23	B
Vest4		0.061
MPC		0.053
ClinPred		0.012	T
GERP RS		-7.1
Varity_R		0.24
gMVP		0.70
Mutation Taster		=97/3	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: rs198977; hg19: chr19-51381777; COSMIC: COSV57568931; COSMIC: COSV57568931;