chr19-50873774-G-A

Variant names:

• chr19-50873774-G-A
• rs2664155
• NM_005551.5:c.46+255G>A

Variant summary

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

The ENST00000325321.8(KLK2):​c.46+255G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 520,062 control chromosomes in the GnomAD database, including 31,249 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 0.32 (8229 hom., cov: 29)
  • Exomes 𝑓: 0.34 (23020 hom.)
• Consequence: KLK2 ENST00000325321.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 12 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000325321.8. 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.46+255G>A		intron	N/A	NP_005542.1
	KLK2	NM_001002231.3		c.46+255G>A		intron	N/A	NP_001002231.1
	KLK2	NM_001256080.2		c.-101+255G>A		intron	N/A	NP_001243009.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK2	ENST00000325321.8	TSL:1 MANE Select	c.46+255G>A		intron	N/A	ENSP00000313581.2
	KLK2	ENST00000358049.8	TSL:1	c.46+255G>A		intron	N/A	ENSP00000350748.3
	KLK2	ENST00000595316.5	TSL:1	n.46+255G>A		intron	N/A	ENSP00000469770.1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48587 AN: 151790 Hom.: 8220 Cov.: 29

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.0701

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.320

GnomAD4 exome AF: 0.340 AC: 125075 AN: 368154 Hom.: 23020 Cov.: 0 AF XY: 0.340 AC XY: 65251 AN XY: 191696

African (AFR) AF: 0.269 AC: 2412 AN: 8952

American (AMR) AF: 0.216 AC: 2786 AN: 12902

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 4150 AN: 11910

East Asian (EAS) AF: 0.0687 AC: 1706 AN: 24826

South Asian (SAS) AF: 0.320 AC: 9709 AN: 30356

European-Finnish (FIN) AF: 0.361 AC: 9831 AN: 27210

Middle Eastern (MID) AF: 0.359 AC: 624 AN: 1738

European-Non Finnish (NFE) AF: 0.379 AC: 86324 AN: 227914

Other (OTH) AF: 0.337 AC: 7533 AN: 22346

GnomAD4 genome AF: 0.320 AC: 48622 AN: 151908 Hom.: 8229 Cov.: 29 AF XY: 0.317 AC XY: 23538 AN XY: 74206

African (AFR) AF: 0.269 AC: 11145 AN: 41420

American (AMR) AF: 0.234 AC: 3574 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1205 AN: 3470

East Asian (EAS) AF: 0.0706 AC: 365 AN: 5168

South Asian (SAS) AF: 0.311 AC: 1491 AN: 4798

European-Finnish (FIN) AF: 0.356 AC: 3761 AN: 10552

Middle Eastern (MID) AF: 0.360 AC: 105 AN: 292

European-Non Finnish (NFE) AF: 0.381 AC: 25903 AN: 67920

Other (OTH) AF: 0.317 AC: 666 AN: 2104

Alfa AF: 0.347 Hom.: 8807

Bravo AF: 0.307

Asia WGS AF: 0.158 AC: 551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.30
DANN	Benign	0.29
PhyloP100		-1.1
PromoterAI		0.0013	Neutral
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: rs2664155; hg19: chr19-51377030;