rs10424878

Positions:

• chr19-50871711-A-G
• chr19-50871711-A-T

Variant summary

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

The ENST00000596950.5(KLK2):​n.113+854A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 152,032 control chromosomes in the GnomAD database, including 27,935 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 0.60 (27935 hom., cov: 32)
• Consequence: KLK2 ENST00000596950.5 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLK2	ENST00000596950.5	n.113+854A>G		intron_variant, non_coding_transcript_variant		1
KLK2	ENST00000593493.5	c.-332-1472A>G		intron_variant		3
KLK2	ENST00000595375.5	n.149+962A>G		intron_variant, non_coding_transcript_variant		4
KLK2	ENST00000597509.5	n.243+854A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91863 AN: 151914 Hom.: 27918 Cov.: 32

Gnomad AFR AF: 0.641

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.785

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.589

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.605 AC: 91922 AN: 152032 Hom.: 27935 Cov.: 32 AF XY: 0.605 AC XY: 44982 AN XY: 74320

Gnomad4 AFR AF: 0.640

Gnomad4 AMR AF: 0.616

Gnomad4 ASJ AF: 0.581

Gnomad4 EAS AF: 0.785

Gnomad4 SAS AF: 0.567

Gnomad4 FIN AF: 0.620

Gnomad4 NFE AF: 0.570

Gnomad4 OTH AF: 0.595

Alfa AF: 0.573 Hom.: 24034

Bravo AF: 0.606

Asia WGS AF: 0.712 AC: 2477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.26
DANN	Benign	0.61

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10424878; hg19: chr19-51374967;