NM_001135629.3(PPP1R21):c.763del (p.Ile255fs) AND Neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities

Germline classification:: Likely pathogenic (1 submission)
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:: RCV003340881.2

Allele description [Variation Report for NM_001135629.3(PPP1R21):c.763del (p.Ile255fs)]

NM_001135629.3(PPP1R21):c.763del (p.Ile255fs)

Gene:

PPP1R21:protein phosphatase 1 regulatory subunit 21 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

2p16.3

Genomic location:

Preferred name:

NM_001135629.3(PPP1R21):c.763del (p.Ile255fs)

HGVS:

NC_000002.12:g.48465508del
NM_001135629.3:c.763delMANE SELECT
NM_001193475.2:c.763del
NM_152994.5:c.763del
NP_001129101.1:p.Ile255fs
NP_001180404.1:p.Ile255fs
NP_694539.1:p.Ile255fs
NC_000002.11:g.48692647del
NR_024188.3:n.990del

Protein change:

I255fs

Molecular consequence:

NM_001135629.3:c.763del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001193475.2:c.763del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_152994.5:c.763del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_024188.3:n.990del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities (NEDHFBA)
Identifiers:: MONDO: MONDO:0859165; MedGen: C5543591; OMIM: 619383

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004047689	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	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

SCV004047689

Neuberg Centre For Genomic Medicine, NCGM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic

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

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 Neuberg Centre For Genomic Medicine, NCGM, SCV004047689.1

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

Description

The c.763del (p.Ile255LeufsTer13) frameshift variant in PPP1R21 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Ile255LeufsTer13 variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant causes a frameshift starting with codon Isoleucine 255, changes this amino acid to Leucine residue, and creates a premature Stop codon at position 13 of the new reading frame, denoted p.Ile255LeufsTer13. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Likely Pathogenic.

#	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: Apr 6, 2024

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