NM_003620.4(PPM1D):c.1237_1238del (p.Pro413fs) AND Intellectual developmental disorder with gastrointestinal difficulties and high pain threshold

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: May 15, 2020
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001175329.3

Allele description [Variation Report for NM_003620.4(PPM1D):c.1237_1238del (p.Pro413fs)]

NM_003620.4(PPM1D):c.1237_1238del (p.Pro413fs)

Gene:

PPM1D:protein phosphatase, Mg2+/Mn2+ dependent 1D [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

17q23.2

Genomic location:

Preferred name:

NM_003620.4(PPM1D):c.1237_1238del (p.Pro413fs)

HGVS:

NC_000017.11:g.60656818_60656819del
NG_023265.1:g.61626_61627del
NM_003620.4:c.1237_1238delMANE SELECT
NP_003611.1:p.Pro413fs
NP_003611.1:p.Pro413fs
LRG_770t1:c.1237_1238del
LRG_770:g.61626_61627del
LRG_770p1:p.Pro413fs
NC_000017.10:g.58734179_58734180del
NM_003620.3:c.1237_1238del
p.Pro413fs

Protein change:

P413fs

Links:

dbSNP: rs1555648565

NCBI 1000 Genomes Browser:

rs1555648565

Molecular consequence:

NM_003620.4:c.1237_1238del - frameshift variant - [Sequence Ontology: SO:0001589]

Functional consequence:

functionally_abnormal [Sequence Ontology: SO:0002218]

Observations:

Condition(s)

Name:: Intellectual developmental disorder with gastrointestinal difficulties and high pain threshold (JDVS)
Synonyms:: JANSEN-DE VRIES SYNDROME
Identifiers:: MONDO: MONDO:0044318; MedGen: C4479517; OMIM: 617450

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001288157	Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	de novo	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002757832	Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (May 15, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001288157

Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic

de novo

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002757832

Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(May 15, 2020)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	de novo	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn, SCV001288157.1

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

Description

By trio-exome sequencing and analysis of the genes with the ten highest PEDIA values (PMID: 31164752) and of genes which could be associated with a developmental delay (n=2539), a pathogenic heterozygous variant in exon 5 of the PPM1D gene could be detected in the patient. The name of the variant is: NM_003620: c.1237_1238del;p.(Pro413Metfs*20). This variant leads to a shift of the reading frame and after 19 wrong amino acids to a premature stop codon . This variant could not be detected in the parents, which is why it is highly probable that the patient developed it anew (de novo). This variant is not recorded in the population-based databases. In the phanotype-related database ClinVar it is once listed as probably pathogenic, in HGMD and LOYD it is not listed. The ACMG classification of this variant is: probably pathogenic (class 4; PS2, PM1, PM2).

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

From Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn, SCV002757832.1

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

#	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		not provided	not provided	not provided	not provided

Last Updated: May 12, 2024

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