NM_001031.5(RPS28):c.1A>G (p.Met1Val) AND Diamond-Blackfan anemia 15 with mandibulofacial dysostosis

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jun 8, 2022
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:: RCV000167573.13

Allele description [Variation Report for NM_001031.5(RPS28):c.1A>G (p.Met1Val)]

NM_001031.5(RPS28):c.1A>G (p.Met1Val)

Gene:

RPS28:ribosomal protein S28 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NM_001031.5(RPS28):c.1A>G (p.Met1Val)

HGVS:

NC_000019.10:g.8321531A>G
NG_028213.2:g.4866T>C
NG_050637.1:g.5032A>G
NM_001031.5:c.1A>GMANE SELECT
NP_001022.1:p.Met1Val
NC_000019.9:g.8386415A>G
NM_001031.4:c.1A>G

Protein change:

M1V; MET1VAL

Links:

OMIM: 603685.0001; dbSNP: rs786203997

NCBI 1000 Genomes Browser:

rs786203997

Molecular consequence:

NM_001031.5:c.1A>G - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001031.5:c.1A>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Diamond-Blackfan anemia 15 with mandibulofacial dysostosis (DBA15)
Identifiers:: MONDO: MONDO:0011639; MedGen: C4225411; Orphanet: 124; OMIM: 606164

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000218453	OMIM	no assertion criteria provided	Pathogenic (Mar 14, 2018)	germline	literature only	Gripp, K. W., Curry, C., Olney, A. H., Sandoval, C., Fisher, J., Chong, J. X.-L., UW Center for Mendelian Genomics, Pilchman, L., Sahraoui, R., Stabley, D. L., Sol-Church, K. Diamond-Blackfan anemia with mandibulofacial dystostosis (sic) is heterogeneous, including the novel DBA genes TSR2 and RPS28. Am. J. Med. Genet. 164A: 2240-2249, 2014.,
SCV000246138	University of Washington Center for Mendelian Genomics, University of Washington	criteria provided, single submitter (Submitter's publication)	Pathogenic (May 19, 2015)	germline	research	PubMed (1) [See all records that cite this PMID]
SCV002526122	Institute of Human Genetics, University Hospital Muenster	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 8, 2022)	unknown	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

SCV000218453

OMIM

no assertion criteria provided

Pathogenic
(Mar 14, 2018)

germline

literature only

Gripp, K. W., Curry, C., Olney, A. H., Sandoval, C., Fisher, J., Chong, J. X.-L., UW Center for Mendelian Genomics, Pilchman, L., Sahraoui, R., Stabley, D. L., Sol-Church, K. Diamond-Blackfan anemia with mandibulofacial dystostosis (sic) is heterogeneous, including the novel DBA genes TSR2 and RPS28. Am. J. Med. Genet. 164A: 2240-2249, 2014.,

SCV000246138

University of Washington Center for Mendelian Genomics, University of Washington

criteria provided, single submitter

(Submitter's publication)

Pathogenic
(May 19, 2015)

germline

research

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

SCV002526122

Institute of Human Genetics, University Hospital Muenster

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jun 8, 2022)

unknown

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	2	not provided	not provided	not provided	not provided	research
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Diamond-Blackfan anemia with mandibulofacial dystostosis is heterogeneous, including the novel DBA genes TSR2 and RPS28.

Gripp KW, Curry C, Olney AH, Sandoval C, Fisher J, Chong JX; UW Center for Mendelian Genomics., Pilchman L, Sahraoui R, Stabley DL, Sol-Church K.

Am J Med Genet A. 2014 Sep;164A(9):2240-9. doi: 10.1002/ajmg.a.36633. Epub 2014 Jun 18.

PubMed [citation]

PMID:: 24942156
PMCID:: PMC4149220

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 OMIM, SCV000218453.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	not provided

Description

In 2 unrelated girls (patients 4 and 5) with Diamond-Blackfan anemia-15 and mandibulofacial dysostosis (DBA15; 606164), Gripp et al. (2014) identified the same de novo heterozygous c.1A-G transition affecting the translation initiation codon of the RPS28 gene (met1 to val), predicted to result in haploinsufficiency. The mutation was found by sequencing of candidate ribosomal protein genes. One of the patients had loss of the mutant allele and SNPs on 19p in peripheral blood cells, but not in buccal DNA, whereas the other patient had loss of the mutant allele and SNPs on 19p in buccal DNA only. It was not known whether this tissue-specific allelic imbalance contributed to the clinical presentation.

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

From University of Washington Center for Mendelian Genomics, University of Washington, SCV000246138.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	research	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		2	not provided	not provided	not provided

From Institute of Human Genetics, University Hospital Muenster, SCV002526122.2

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

Description

ACMG categories: PVS1,PS1,PP5

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

Last Updated: Aug 25, 2024

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