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NM_001022.4(RPS19):c.353A>G (p.Asp118Gly) AND Diamond-Blackfan anemia

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
May 13, 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:
RCV004556141.1

Allele description [Variation Report for NM_001022.4(RPS19):c.353A>G (p.Asp118Gly)]

NM_001022.4(RPS19):c.353A>G (p.Asp118Gly)

Genes:
MIR6797:microRNA 6797 [Gene - HGNC]
RPS19:ribosomal protein S19 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19q13.2
Genomic location:
Preferred name:
NM_001022.4(RPS19):c.353A>G (p.Asp118Gly)
Other names:
NM_001321485.2:c.366A>G
HGVS:
  • NC_000019.10:g.41869211A>G
  • NG_007080.3:g.14294A>G
  • NM_001022.4:c.353A>GMANE SELECT
  • NM_001321483.2:c.353A>G
  • NM_001321484.2:c.353A>G
  • NM_001321485.2:c.366A>G
  • NP_001013.1:p.Asp118Gly
  • NP_001308412.1:p.Asp118Gly
  • NP_001308413.1:p.Asp118Gly
  • NP_001308414.1:p.Arg122=
  • LRG_1144t1:c.353A>G
  • LRG_1144:g.14294A>G
  • LRG_1144p1:p.Asp118Gly
  • NC_000019.9:g.42373281A>G
Protein change:
D118G
Molecular consequence:
  • NM_001022.4:c.353A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001321483.2:c.353A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001321484.2:c.353A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001321485.2:c.366A>G - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:
Diamond-Blackfan anemia
Synonyms:
Blackfan Diamond syndrome; Anemia congenital erythroid hypoplastic; Aregenerative anemia chronic congenital; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015253; MeSH: D029503; MedGen: C1260899; Orphanet: 124; OMIM: PS105650; Human Phenotype Ontology: HP:0004810

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV005045272Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely Pathogenic
(May 13, 2024) 		germlinecuration

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Citations

PubMed

A functional assay for the clinical annotation of genetic variants of uncertain significance in Diamond-Blackfan anemia.

Aspesi A, Betti M, Sculco M, Actis C, Olgasi C, Wlodarski MW, Vlachos A, Lipton JM, Ramenghi U, Santoro C, Follenzi A, Ellis SR, Dianzani I.

Hum Mutat. 2018 Aug;39(8):1102-1111. doi: 10.1002/humu.23551. Epub 2018 May 28.

PubMed [citation]
PMID:
29766597
PMCID:
PMC6055729

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 Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV005045272.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (2)

Description

The heterozygous p.Asp118Gly variant in RPS19 was identified by our study in one individual with Diamond-Blackfan anemia. This variant is assumed de novo in the individual, but maternity and paternity have not been confirmed. This variant was reported in one individual with Diamond-Blackfan anemia, and was absent from large population studies (PMID: 25424902). This variant is assumed de novo in the individual, but maternity and paternity have not been confirmed (PMID: 25424902). The number of reported affected individuals with this variant is slightly greater than expected compared to non-affected individuals with this variant. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In vitro functional studies provide some evidence that the p.Asp118Gly variant may impact protein function in patient cells (PMID: 29766597). However, these types of assays may not accurately represent biological function. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for autosomal dominant Diamond-Blackfan anemia. ACMG/AMP Criteria applied: PS4_Supporting, PM6, PM2_Supporting, PP3, PS3_Moderate (Richards 2015).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 8, 2024