NM_001171613.2(PREPL):c.1595A>G (p.Lys532Arg) AND not provided

Germline classification:: Likely benign (2 submissions)
Last evaluated:: Jul 1, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000553009.32

Allele description [Variation Report for NM_001171613.2(PREPL):c.1595A>G (p.Lys532Arg)]

NM_001171613.2(PREPL):c.1595A>G (p.Lys532Arg)

Gene:

PREPL:prolyl endopeptidase like [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p21

Genomic location:

Preferred name:

NM_001171613.2(PREPL):c.1595A>G (p.Lys532Arg)

HGVS:

NC_000002.12:g.44323296T>C
NG_016429.1:g.43567A>G
NM_001042385.2:c.1676A>G
NM_001042386.2:c.1664A>G
NM_001171603.1:c.1862A>G
NM_001171606.2:c.1862A>G
NM_001171613.2:c.1595A>GMANE SELECT
NM_001171617.1:c.1595A>G
NM_001374275.1:c.1862A>G
NM_001374276.1:c.1862A>G
NM_001374277.1:c.1595A>G
NM_006036.4:c.1862A>G
NP_001035844.1:p.Lys559Arg
NP_001035845.1:p.Lys555Arg
NP_001165074.1:p.Lys621Arg
NP_001165077.1:p.Lys621Arg
NP_001165084.1:p.Lys532Arg
NP_001165088.1:p.Lys532Arg
NP_001361204.1:p.Lys621Arg
NP_001361205.1:p.Lys621Arg
NP_001361206.1:p.Lys532Arg
NP_006027.2:p.Lys621Arg
NC_000002.11:g.44550435T>C

Protein change:

K532R

Links:

dbSNP: rs111438719

NCBI 1000 Genomes Browser:

rs111438719

Molecular consequence:

NM_001042385.2:c.1676A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001042386.2:c.1664A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001171603.1:c.1862A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001171606.2:c.1862A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001171613.2:c.1595A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001171617.1:c.1595A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001374275.1:c.1862A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001374276.1:c.1862A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001374277.1:c.1595A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_006036.4:c.1862A>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001152249	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Likely benign (Jul 1, 2024)	germline	clinical testing	Citation Link,
SCV001550579	Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR) See additional submitters Franklin by Genoox	no assertion criteria provided	Likely benign	unknown	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001152249

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Likely benign
(Jul 1, 2024)

germline

clinical testing

Citation Link,

SCV001550579

Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria provided

Likely benign

unknown

clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	4	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From CeGaT Center for Human Genetics Tuebingen, SCV001152249.32

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	4	not provided	not provided	clinical testing	not provided

Description

PREPL: BP4, BS2

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		4	not provided	not provided	not provided

From Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV001550579.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The PREPL p.Lys532Arg variant was not identified in the literature but was identified in dbSNP (ID: rs111438719) and ClinVar (classified as likely benign by Invitae and as uncertain significance by CeGaT Praxis fuer Humangenetik Tuebingen). The variant was identified in control databases in 433 of 280810 chromosomes (1 homozygous) at a frequency of 0.001542 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: Ashkenazi Jewish in 60 of 10336 chromosomes (freq: 0.005805), Latino in 142 of 35010 chromosomes (freq: 0.004056), African in 84 of 24904 chromosomes (freq: 0.003373), Other in 18 of 7174 chromosomes (freq: 0.002509), European (non-Finnish) in 116 of 128520 chromosomes (freq: 0.000903) and South Asian in 13 of 30024 chromosomes (freq: 0.000433), but was not observed in the East Asian or European (Finnish) populations. The p.Lys532 residue is conserved in mammals but not in more distantly related organisms however four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 22, 2025

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