NM_000969.5(RPL5):c.587G>A (p.Arg196Gln) AND Diamond-Blackfan anemia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 21, 2020
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:: RCV002041441.14

Allele description [Variation Report for NM_000969.5(RPL5):c.587G>A (p.Arg196Gln)]

NM_000969.5(RPL5):c.587G>A (p.Arg196Gln)

Genes:

DIPK1A:divergent protein kinase domain 1A [Gene - OMIM - HGNC]
RPL5:ribosomal protein L5 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p22.1

Genomic location:

Preferred name:

NM_000969.5(RPL5):c.587G>A (p.Arg196Gln)

HGVS:

NC_000001.11:g.92837515G>A
NG_011779.2:g.10530G>A
NG_033051.1:g.129008C>T
NM_000969.5:c.587G>AMANE SELECT
NM_001252273.2:c.475-4481C>T
NP_000960.2:p.Arg196Gln
LRG_1155t1:c.587G>A
LRG_1155:g.10530G>A
LRG_1155p1:p.Arg196Gln
NC_000001.10:g.93303072G>A
NR_146333.1:n.646G>A

Protein change:

R196Q

Links:

dbSNP: rs771013653

NCBI 1000 Genomes Browser:

rs771013653

Molecular consequence:

NM_001252273.2:c.475-4481C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000969.5:c.587G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_146333.1:n.646G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002110399	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 21, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30503522, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002110399

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 21, 2020)

germline

clinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

The Genetic Landscape of Diamond-Blackfan Anemia.

Ulirsch JC, Verboon JM, Kazerounian S, Guo MH, Yuan D, Ludwig LS, Handsaker RE, Abdulhay NJ, Fiorini C, Genovese G, Lim ET, Cheng A, Cummings BB, Chao KR, Beggs AH, Genetti CA, Sieff CA, Newburger PE, Niewiadomska E, Matysiak M, Vlachos A, Lipton JM, et al.

Am J Hum Genet. 2018 Dec 6;103(6):930-947. doi: 10.1016/j.ajhg.2018.10.027. Epub 2018 Nov 29. Erratum in: Am J Hum Genet. 2019 Feb 7;104(2):356. doi: 10.1016/j.ajhg.2018.12.011.

PubMed [citation]

PMID:: 30503522
PMCID:: PMC6288280

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002110399.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant is present in population databases (rs771013653, ExAC 0.01%). This sequence change replaces arginine with glutamine at codon 196 of the RPL5 protein (p.Arg196Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has been observed in individual(s) with clinical features of Diamond-Blackfan anemia (PMID: 30503522).

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

Last Updated: Nov 3, 2024

ClinVar

Relating variation to medicine