NM_005551.5:c.372C>A

Variant names:

• chr19-50876637-C-A
• rs198972
• NM_005551.5:c.372C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_005551.5(KLK2):​c.372C>A​(p.Leu124Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: KLK2 NM_005551.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29
• Publications: 31 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP7: Synonymous conserved (PhyloP=-2.29 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005551.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK2	NM_005551.5	MANE Select	c.372C>A	p.Leu124Leu	synonymous	Exon 3 of 5	NP_005542.1
	KLK2	NM_001002231.3		c.372C>A	p.Leu124Leu	synonymous	Exon 3 of 5	NP_001002231.1
	KLK2	NM_001256080.2		c.66C>A	p.Leu22Leu	synonymous	Exon 2 of 4	NP_001243009.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK2	ENST00000325321.8	TSL:1 MANE Select	c.372C>A	p.Leu124Leu	synonymous	Exon 3 of 5	ENSP00000313581.2
	KLK2	ENST00000358049.8	TSL:1	c.372C>A	p.Leu124Leu	synonymous	Exon 3 of 5	ENSP00000350748.3
	KLK2	ENST00000595316.5	TSL:1	n.*62C>A		non_coding_transcript_exon	Exon 2 of 3	ENSP00000469770.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 48

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.3
DANN	Benign	0.52
PhyloP100		-2.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs198972; hg19: chr19-51379893;