chr19-50873774-G-A

Position:

• chr19-50873774-G-A

Variant summary

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

The NM_005551.5(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 NM_005551.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLK2	NM_005551.5	c.46+255G>A		intron_variant		ENST00000325321.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLK2	ENST00000325321.8	c.46+255G>A		intron_variant		1	NM_005551.5	P1

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

Gnomad4 AFR exome AF: 0.269

Gnomad4 AMR exome AF: 0.216

Gnomad4 ASJ exome AF: 0.348

Gnomad4 EAS exome AF: 0.0687

Gnomad4 SAS exome AF: 0.320

Gnomad4 FIN exome AF: 0.361

Gnomad4 NFE exome AF: 0.379

Gnomad4 OTH exome AF: 0.337

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

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.0706

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.381

Gnomad4 OTH AF: 0.317

Alfa AF: 0.362 Hom.: 3499

Bravo AF: 0.307

Asia WGS AF: 0.158 AC: 551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.30
DANN	Benign	0.29

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: rs2664155; hg19: chr19-51377030;