NM_001014.5(RPS10):c.337C>T (p.Arg113Ter) AND Diamond-Blackfan anemia

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 25, 2021
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:: RCV001851701.7

Allele description [Variation Report for NM_001014.5(RPS10):c.337C>T (p.Arg113Ter)]

NM_001014.5(RPS10):c.337C>T (p.Arg113Ter)

Genes:

RPS10-NUDT3:RPS10-NUDT3 readthrough [Gene - HGNC]
RPS10:ribosomal protein S10 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p21.31

Genomic location:

Preferred name:

NM_001014.5(RPS10):c.337C>T (p.Arg113Ter)

HGVS:

NC_000006.12:g.34421793G>A
NG_023200.1:g.9307C>T
NM_001014.5:c.337C>TMANE SELECT
NM_001202470.3:c.337C>T
NM_001203245.3:c.337C>T
NM_001204091.2:c.337C>T
NP_001005.1:p.Arg113Ter
NP_001189399.1:p.Arg113Ter
NP_001190174.1:p.Arg113Ter
NP_001191020.1:p.Arg113Ter
LRG_1138t1:c.337C>T
LRG_1138:g.9307C>T
LRG_1138p1:p.Arg113Ter
NC_000006.11:g.34389570G>A
NM_001014.4:c.337C>T

Protein change:

R113*; ARG113TER

Links:

OMIM: 603632.0003; dbSNP: rs267607022

NCBI 1000 Genomes Browser:

rs267607022

Molecular consequence:

NM_001014.5:c.337C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001202470.3:c.337C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001203245.3:c.337C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001204091.2:c.337C>T - nonsense - [Sequence Ontology: SO:0001587]

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

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PREDICTED: Mus musculus striatin interacting protein 2 (Strip2), transcript vari...
PREDICTED: Mus musculus striatin interacting protein 2 (Strip2), transcript variant X1, mRNA
gi|1720418232|ref|XM_006505118.4|

Nucleotide
RecName: Full=Striatin-interacting proteins 2; AltName: Full=Protein FAM40B
RecName: Full=Striatin-interacting proteins 2; AltName: Full=Protein FAM40B
gi|71151882|sp|Q8C9H6.1|STRP2_MOUSE

Protein
GO597_RS00855 [Sulfolobus acidocaldarius DSM 639]
GO597_RS00855 [Sulfolobus acidocaldarius DSM 639]
Gene ID:78440326

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002243462	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 25, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23718193, 20116044, 28492532
SCV002618200	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Jan 14, 2019)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 20116044, 23718193 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002243462

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 25, 2021)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV002618200

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Jan 14, 2019)

germline

clinical testing

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

Citation Link

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

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

Ribosomal protein genes RPS10 and RPS26 are commonly mutated in Diamond-Blackfan anemia.

Doherty L, Sheen MR, Vlachos A, Choesmel V, O'Donohue MF, Clinton C, Schneider HE, Sieff CA, Newburger PE, Ball SE, Niewiadomska E, Matysiak M, Glader B, Arceci RJ, Farrar JE, Atsidaftos E, Lipton JM, Gleizes PE, Gazda HT.

Am J Hum Genet. 2010 Feb 12;86(2):222-8. doi: 10.1016/j.ajhg.2009.12.015. Epub 2010 Jan 28. Erratum in: Am J Hum Genet. 2010 Apr 9;86(4):655.

PubMed [citation]

PMID:: 20116044
PMCID:: PMC2820177

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002243462.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Arg113*) in the RPS10 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RPS10 are known to be pathogenic (PMID: 20116044, 23718193). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 6187). This premature translational stop signal has been observed in individual(s) with Diamond-Blackfan anemia (PMID: 20116044). This variant is not present in population databases (ExAC no frequency).

#	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

From Ambry Genetics, SCV002618200.2

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

Description

The p.R113* pathogenic mutation (also known as c.337C>T), located in coding exon 3 of the RPS10 gene, results from a C to T substitution at nucleotide position 337. This changes the amino acid from an arginine to a stop codon within coding exon 3. This mutation was identified in multiple individuals with Diamond-Blackfan anemia (Doherty L et al. Am. J. Hum. Genet., 2010 Feb;86:222-8; Gerrard G et al. Br. J. Haematol., 2013 Aug;162:530-6). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#	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: Sep 29, 2024

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