19-50879944-G-T

Position:

• chr19-50879944-G-T

Variant summary

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

The NM_005551.5(KLK2):​c.*1385G>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 0.059 in 230,276 control chromosomes in the GnomAD database, including 515 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 0.058 (338 hom., cov: 32)
  • Exomes 𝑓: 0.061 (177 hom.)
• Consequence: KLK2 NM_005551.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.738

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLK2	NM_005551.5	c.*1385G>T		3_prime_UTR_variant	5/5	ENST00000325321.8	NP_005542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK2	ENST00000325321.8	c.*1385G>T		3_prime_UTR_variant	5/5	1	NM_005551.5	ENSP00000313581	P1
KLK2	ENST00000358049.8	c.*1536G>T		3_prime_UTR_variant	5/5	1		ENSP00000350748
KLK2	ENST00000597439.1	c.*1700G>T		3_prime_UTR_variant, NMD_transcript_variant	5/5	1		ENSP00000471214
KLK2	ENST00000391810.6	c.*1385G>T		3_prime_UTR_variant	4/4	2		ENSP00000375686

Frequencies

GnomAD3 genomes AF: 0.0581 AC: 8842 AN: 152160 Hom.: 338 Cov.: 32

Gnomad AFR AF: 0.0149

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.0496

Gnomad ASJ AF: 0.0652

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0163

Gnomad FIN AF: 0.0851

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0878

Gnomad OTH AF: 0.0593

GnomAD4 exome AF: 0.0607 AC: 4735 AN: 77998 Hom.: 177 Cov.: 0 AF XY: 0.0610 AC XY: 2189 AN XY: 35886

Gnomad4 AFR exome AF: 0.0127

Gnomad4 AMR exome AF: 0.0365

Gnomad4 ASJ exome AF: 0.0583

Gnomad4 EAS exome AF: 0.0000905

Gnomad4 SAS exome AF: 0.0207

Gnomad4 FIN exome AF: 0.107

Gnomad4 NFE exome AF: 0.0798

Gnomad4 OTH exome AF: 0.0655

GnomAD4 genome AF: 0.0581 AC: 8845 AN: 152278 Hom.: 338 Cov.: 32 AF XY: 0.0564 AC XY: 4199 AN XY: 74462

Gnomad4 AFR AF: 0.0148

Gnomad4 AMR AF: 0.0496

Gnomad4 ASJ AF: 0.0652

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0168

Gnomad4 FIN AF: 0.0851

Gnomad4 NFE AF: 0.0878

Gnomad4 OTH AF: 0.0587

Alfa AF: 0.0392 Hom.: 28

Bravo AF: 0.0540

Asia WGS AF: 0.0110 AC: 38 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.2
DANN	Benign	0.69

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: rs80050017; hg19: chr19-51383200;