NM_000996.4(RPL35A):c.125A>G (p.Tyr42Cys) AND Diamond-Blackfan anemia 5

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 11, 2023
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:: RCV003514552.1

Allele description [Variation Report for NM_000996.4(RPL35A):c.125A>G (p.Tyr42Cys)]

NM_000996.4(RPL35A):c.125A>G (p.Tyr42Cys)

Genes:

IQCG:IQ motif containing G [Gene - OMIM - HGNC]
RPL35A:ribosomal protein L35a [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3q29

Genomic location:

Preferred name:

NM_000996.4(RPL35A):c.125A>G (p.Tyr42Cys)

HGVS:

NC_000003.12:g.197951272A>G
NG_011743.1:g.6092A>G
NG_033072.1:g.13744T>C
NM_000996.4:c.125A>GMANE SELECT
NM_001316311.2:c.125A>G
NM_001323028.2:c.-49-7221T>C
NM_001323029.2:c.-374-5586T>C
NM_032263.5:c.-59-5586T>CMANE SELECT
NP_000987.2:p.Tyr42Cys
NP_001303240.1:p.Tyr42Cys
LRG_1129t1:c.125A>G
LRG_1129:g.6092A>G
LRG_1129p1:p.Tyr42Cys
NC_000003.11:g.197678143A>G
NM_000996.2:c.125A>G

Protein change:

Y42C

Molecular consequence:

NM_001323028.2:c.-49-7221T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001323029.2:c.-374-5586T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_032263.5:c.-59-5586T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000996.4:c.125A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001316311.2:c.125A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Diamond-Blackfan anemia 5 (DBA5)
Identifiers:: MONDO: MONDO:0012925; MedGen: C2675859; Orphanet: 124; OMIM: 612528

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004292263	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 11, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25424902, 29146883, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004292263

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 11, 2023)

germline

clinical testing

PubMed (3)
[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

Loss of function mutations in RPL27 and RPS27 identified by whole-exome sequencing in Diamond-Blackfan anaemia.

Wang R, Yoshida K, Toki T, Sawada T, Uechi T, Okuno Y, Sato-Otsubo A, Kudo K, Kamimaki I, Kanezaki R, Shiraishi Y, Chiba K, Tanaka H, Terui K, Sato T, Iribe Y, Ohga S, Kuramitsu M, Hamaguchi I, Ohara A, Hara J, Goi K, et al.

Br J Haematol. 2015 Mar;168(6):854-64. doi: 10.1111/bjh.13229. Epub 2014 Nov 25.

PubMed [citation]

PMID:: 25424902

A landscape of germ line mutations in a cohort of inherited bone marrow failure patients.

Bluteau O, Sebert M, Leblanc T, Peffault de Latour R, Quentin S, Lainey E, Hernandez L, Dalle JH, Sicre de Fontbrune F, Lengline E, Itzykson R, Clappier E, Boissel N, Vasquez N, Da Costa M, Masliah-Planchon J, Cuccuini W, Raimbault A, De Jaegere L, Adès L, Fenaux P, Maury S, et al.

Blood. 2018 Feb 15;131(7):717-732. doi: 10.1182/blood-2017-09-806489. Epub 2017 Nov 16.

PubMed [citation]

PMID:: 29146883

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV004292263.1

#	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 replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 42 of the RPL35A protein (p.Tyr42Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with RPL35A-related condition (PMID: 25424902, 29146883). ClinVar contains an entry for this variant (Variation ID: 1723464). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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.

#	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: May 12, 2024

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