19-50873907-T-C

Variant names:

• chr19-50873907-T-C
• rs2664156
• NM_005551.5:c.46+388T>C

Variant summary

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

The NM_005551.5(KLK2):​c.46+388T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 202,604 control chromosomes in the GnomAD database, including 63,558 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 0.79 (47763 hom., cov: 30)
  • Exomes 𝑓: 0.78 (15795 hom.)
• Consequence: KLK2 NM_005551.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.46
• Publications: 8 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLK2	NM_005551.5	c.46+388T>C		intron_variant	Intron 1 of 4	ENST00000325321.8	NP_005542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK2	ENST00000325321.8	c.46+388T>C		intron_variant	Intron 1 of 4	1	NM_005551.5	ENSP00000313581.2

Frequencies

GnomAD3 genomes AF: 0.792 AC: 120282 AN: 151860 Hom.: 47725 Cov.: 30

Gnomad AFR AF: 0.795

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.794

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.886

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.784

Gnomad OTH AF: 0.772

GnomAD4 exome AF: 0.785 AC: 39732 AN: 50626 Hom.: 15795 Cov.: 0 AF XY: 0.785 AC XY: 20368 AN XY: 25930

African (AFR) AF: 0.793 AC: 1199 AN: 1512

American (AMR) AF: 0.721 AC: 1842 AN: 2556

Ashkenazi Jewish (ASJ) AF: 0.786 AC: 1567 AN: 1994

East Asian (EAS) AF: 0.866 AC: 2742 AN: 3168

South Asian (SAS) AF: 0.730 AC: 1741 AN: 2386

European-Finnish (FIN) AF: 0.889 AC: 2455 AN: 2762

Middle Eastern (MID) AF: 0.750 AC: 207 AN: 276

European-Non Finnish (NFE) AF: 0.779 AC: 25410 AN: 32624

Other (OTH) AF: 0.767 AC: 2569 AN: 3348

GnomAD4 genome AF: 0.792 AC: 120370 AN: 151978 Hom.: 47763 Cov.: 30 AF XY: 0.794 AC XY: 59013 AN XY: 74290

African (AFR) AF: 0.794 AC: 32909 AN: 41422

American (AMR) AF: 0.751 AC: 11468 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.794 AC: 2755 AN: 3470

East Asian (EAS) AF: 0.842 AC: 4347 AN: 5164

South Asian (SAS) AF: 0.757 AC: 3636 AN: 4806

European-Finnish (FIN) AF: 0.886 AC: 9389 AN: 10598

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.784 AC: 53257 AN: 67942

Other (OTH) AF: 0.776 AC: 1633 AN: 2104

Alfa AF: 0.781 Hom.: 141721

Bravo AF: 0.782

Asia WGS AF: 0.810 AC: 2818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.93
DANN	Benign	0.42
PhyloP100		-4.5
PromoterAI		-0.0018	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: rs2664156; hg19: chr19-51377163;