NM_006796.3(AFG3L2):c.571G>A (p.Val191Ile) AND not provided

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Aug 1, 2023
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:: RCV001756119.8

Allele description [Variation Report for NM_006796.3(AFG3L2):c.571G>A (p.Val191Ile)]

NM_006796.3(AFG3L2):c.571G>A (p.Val191Ile)

Gene:

AFG3L2:AFG3 like matrix AAA peptidase subunit 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

18p11.21

Genomic location:

Preferred name:

NM_006796.3(AFG3L2):c.571G>A (p.Val191Ile)

HGVS:

NC_000018.10:g.12363838C>T
NG_023361.1:g.18439G>A
NM_006796.3:c.571G>AMANE SELECT
NP_006787.2:p.Val191Ile
NP_006787.2:p.Val191Ile
LRG_666t1:c.571G>A
LRG_666:g.18439G>A
LRG_666p1:p.Val191Ile
NC_000018.9:g.12363837C>T
NM_006796.2:c.571G>A

Protein change:

V191I

Links:

dbSNP: rs1373473541

NCBI 1000 Genomes Browser:

rs1373473541

Molecular consequence:

NM_006796.3:c.571G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Chronic lymphocytic leukemia: peripheral blood B cells (HG-U133B)
Chronic lymphocytic leukemia: peripheral blood B cells (HG-U133B)
Accession: GDS4168

GEO DataSets
Related DataSets for GEO Profiles (Select 81434599) (1)
GEO DataSets

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
SCV001985526	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Sep 6, 2019)	germline	clinical testing	Citation Link,
SCV003442577	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 1, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26454370, 28492532
SCV004137727	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Uncertain significance (Aug 1, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001985526

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Sep 6, 2019)

germline

clinical testing

Citation Link,

SCV003442577

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 1, 2022)

germline

clinical testing

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

SCV004137727

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Uncertain significance
(Aug 1, 2023)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A novel AFG3L2 mutation in a Somalian patient with spinocerebellar ataxia type 28.

Qu J, Wu CK, Zuzuárregui JR, Hohler AD.

J Neurol Sci. 2015 Nov 15;358(1-2):530-1. doi: 10.1016/j.jns.2015.10.003. Epub 2015 Oct 3. No abstract available.

PubMed [citation]

PMID:: 26454370

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From GeneDx, SCV001985526.2

#	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, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 28660440, 26454370)

#	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 Invitae, SCV003442577.1

#	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 valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 191 of the AFG3L2 protein (p.Val191Ile). This variant is present in population databases (no rsID available, gnomAD 0.009%). This missense change has been observed in individual(s) with spinocerebellar ataxia (PMID: 26454370). ClinVar contains an entry for this variant (Variation ID: 548568). 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 tolerated. 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 CeGaT Center for Human Genetics Tuebingen, SCV004137727.5

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

#	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		1	not provided	not provided	not provided

Last Updated: May 12, 2024

ClinVar

Relating variation to medicine