NM_015713.5(RRM2B):c.786G>T (p.Glu262Asp) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 23, 2022
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:: RCV001879920.4

Allele description [Variation Report for NM_015713.5(RRM2B):c.786G>T (p.Glu262Asp)]

NM_015713.5(RRM2B):c.786G>T (p.Glu262Asp)

Gene:

RRM2B:ribonucleotide reductase regulatory TP53 inducible subunit M2B [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q22.3

Genomic location:

Preferred name:

NM_015713.5(RRM2B):c.786G>T (p.Glu262Asp)

HGVS:

NC_000008.11:g.102214057C>A
NG_016617.1:g.30062G>T
NM_001172477.1:c.1002G>T
NM_001172478.2:c.630G>T
NM_015713.5:c.786G>TMANE SELECT
NP_001165948.1:p.Glu334Asp
NP_001165949.1:p.Glu210Asp
NP_056528.2:p.Glu262Asp
LRG_788t1:c.1002G>T
LRG_788t2:c.786G>T
LRG_788:g.30062G>T
LRG_788p1:p.Glu334Asp
NC_000008.10:g.103226285C>A
NC_000008.10:g.103226285C>A
NM_015713.4:c.786G>T

Protein change:

E210D; GLU262ASP

Links:

OMIM: 604712.0016; dbSNP: rs1810682433

NCBI 1000 Genomes Browser:

rs1810682433

Molecular consequence:

NM_001172477.1:c.1002G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001172478.2:c.630G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_015713.5:c.786G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002262131	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 23, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 32827185, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002262131

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 23, 2022)

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

Renal dysfunction, rod-cone dystrophy, and sensorineural hearing loss caused by a mutation in RRM2B.

Roberts L, Julius S, Dawlat S, Yildiz S, Rebello G, Meldau S, Pillay K, Esterhuizen A, Vorster A, Benefeld G, da Rocha J, Beighton P, Sellars SL, Thandrayen K, Pettifor JM, Ramesar RS.

Hum Mutat. 2020 Nov;41(11):1871-1876. doi: 10.1002/humu.24094. Epub 2020 Sep 9.

PubMed [citation]

PMID:: 32827185

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 Invitae, SCV002262131.3

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

Description

This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 262 of the RRM2B protein (p.Glu262Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of autosomal recessive mitochondrial DNA depletion syndrome (PMID: 32827185). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 977276). 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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