NM_032380.5(GFM2):c.1728T>A (p.Asp576Glu) AND not provided

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Mar 14, 2024
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:: RCV000196748.18

Allele description [Variation Report for NM_032380.5(GFM2):c.1728T>A (p.Asp576Glu)]

NM_032380.5(GFM2):c.1728T>A (p.Asp576Glu)

Gene:

GFM2:GTP dependent ribosome recycling factor mitochondrial 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q13.3

Genomic location:

Preferred name:

NM_032380.5(GFM2):c.1728T>A (p.Asp576Glu)

Other names:

p.D576E:GAT>GAA

HGVS:

NC_000005.10:g.74726125A>T
NG_011531.1:g.46093T>A
NM_001281302.2:c.1824T>A
NM_032380.5:c.1728T>AMANE SELECT
NM_170691.3:c.1587T>A
NP_001268231.1:p.Asp608Glu
NP_115756.2:p.Asp576Glu
NP_733792.1:p.Asp529Glu
NC_000005.9:g.74021950A>T
NM_032380.3:c.1728T>A
NM_032380.4:c.1728T>A
NM_170681.1:c.*10639T>A
NR_104006.2:n.1793T>A

Protein change:

D529E; ASP576GLU

Links:

OMIM: 606544.0001; dbSNP: rs140077535

NCBI 1000 Genomes Browser:

rs140077535

Molecular consequence:

NM_001281302.2:c.1824T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_032380.5:c.1728T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_170691.3:c.1587T>A - missense variant - [Sequence Ontology: SO:0001583]
NR_104006.2:n.1793T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV000251581	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Mar 14, 2024)	germline	clinical testing	Citation Link,
SCV002222089	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 2, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22700954, 28492532
SCV005188627	Breakthrough Genomics, Breakthrough Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance	germline	not provided	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000251581

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Mar 14, 2024)

germline

clinical testing

Citation Link,

SCV002222089

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 2, 2024)

germline

clinical testing

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

SCV005188627

Breakthrough Genomics, Breakthrough Genomics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance

germline

not provided

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Exome sequencing can improve diagnosis and alter patient management.

Dixon-Salazar TJ, Silhavy JL, Udpa N, Schroth J, Bielas S, Schaffer AE, Olvera J, Bafna V, Zaki MS, Abdel-Salam GH, Mansour LA, Selim L, Abdel-Hadi S, Marzouki N, Ben-Omran T, Al-Saana NA, Sonmez FM, Celep F, Azam M, Hill KJ, Collazo A, Fenstermaker AG, et al.

Sci Transl Med. 2012 Jun 13;4(138):138ra78. doi: 10.1126/scitranslmed.3003544.

PubMed [citation]

PMID:: 22700954
PMCID:: PMC4442637

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

See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV000251581.16

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 38283147, 26016410, 22700954)

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002222089.3

#	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 aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 576 of the GFM2 protein (p.Asp576Glu). This variant is present in population databases (rs140077535, gnomAD 0.3%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with a neurodevelopmental disorder and insulin-dependent diabetes (PMID: 22700954). ClinVar contains an entry for this variant (Variation ID: 55856). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests 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

From Breakthrough Genomics, Breakthrough Genomics, SCV005188627.1

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

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

Last Updated: Oct 26, 2024

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