ENST00000596950.5:n.113+854A>G

Variant names:

• chr19-50871711-A-G
• rs10424878
• ENST00000596950.5:n.113+854A>G

Variant summary

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

The ENST00000596950.5(KLK2):​n.113+854A>G variant causes a intron 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 13 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=-0.98).
• 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK2	ENST00000596950.5	n.113+854A>G		intron_variant	Intron 1 of 3	1
KLK2	ENST00000593493.5	c.-332-1472A>G		intron_variant	Intron 1 of 3	3		ENSP00000472852.1
KLK2	ENST00000595375.5	n.149+962A>G		intron_variant	Intron 1 of 2	4
KLK2	ENST00000597509.5	n.243+854A>G		intron_variant	Intron 1 of 3	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

African (AFR) AF: 0.640 AC: 26542 AN: 41442

American (AMR) AF: 0.616 AC: 9422 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.581 AC: 2013 AN: 3466

East Asian (EAS) AF: 0.785 AC: 4060 AN: 5174

South Asian (SAS) AF: 0.567 AC: 2728 AN: 4814

European-Finnish (FIN) AF: 0.620 AC: 6543 AN: 10554

Middle Eastern (MID) AF: 0.473 AC: 138 AN: 292

European-Non Finnish (NFE) AF: 0.570 AC: 38736 AN: 67978

Other (OTH) AF: 0.595 AC: 1252 AN: 2104

Alfa AF: 0.582 Hom.: 71974

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
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs10424878; hg19: chr19-51374967;