NM_030962.4(SBF2):c.3290C>A (p.Thr1097Asn) AND Charcot-Marie-Tooth disease type 4B2

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Sep 6, 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:: RCV001114470.9

Allele description [Variation Report for NM_030962.4(SBF2):c.3290C>A (p.Thr1097Asn)]

NM_030962.4(SBF2):c.3290C>A (p.Thr1097Asn)

Genes:

SBF2:SET binding factor 2 [Gene - OMIM - HGNC]
LOC101928008:uncharacterized LOC101928008 [Gene]

Variant type:

single nucleotide variant

Cytogenetic location:

11p15.4

Genomic location:

Preferred name:

NM_030962.4(SBF2):c.3290C>A (p.Thr1097Asn)

HGVS:

NC_000011.10:g.9839663G>T
NG_008074.1:g.459545C>A
NM_001386339.1:c.3290C>A
NM_001386342.1:c.3161C>A
NM_030962.4:c.3290C>AMANE SELECT
NP_001373268.1:p.Thr1097Asn
NP_001373271.1:p.Thr1054Asn
NP_112224.1:p.Thr1097Asn
NP_112224.1:p.Thr1097Asn
LRG_267t1:c.3290C>A
LRG_267:g.459545C>A
LRG_267p1:p.Thr1097Asn
NC_000011.9:g.9861210G>T
NM_030962.3:c.3290C>A
p.Thr1097Asn

Protein change:

T1054N

Links:

dbSNP: rs141894081

NCBI 1000 Genomes Browser:

rs141894081

Molecular consequence:

NM_001386339.1:c.3290C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001386342.1:c.3161C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_030962.4:c.3290C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Charcot-Marie-Tooth disease type 4B2
Synonyms:: CHARCOT-MARIE-TOOTH DISEASE, WITH FOCALLY FOLDED MYELIN SHEATHS, AUTOSOMAL RECESSIVE, TYPE 4B2; CMT 4B2; CHARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, TYPE 4B2; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011475; MedGen: C1858278; Orphanet: 99956; OMIM: 604563

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001272357	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Jan 12, 2018)	germline	clinical testing	Citation Link,
SCV001440509	Institute of Human Genetics, University of Leipzig Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jan 1, 2019)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003799442	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024)	Uncertain significance (Sep 6, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001272357

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Uncertain significance
(Jan 12, 2018)

germline

clinical testing

Citation Link,

SCV001440509

Institute of Human Genetics, University of Leipzig Medical Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jan 1, 2019)

unknown

clinical testing

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

SCV003799442

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process 2024)

Uncertain significance
(Sep 6, 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	unknown	yes	not provided	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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Illumina Laboratory Services, Illumina, SCV001272357.1

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

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

#	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 Institute of Human Genetics, University of Leipzig Medical Center, SCV001440509.1

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

Description

This variant was identified as compound heterozygous.

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

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV003799442.3

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

Description

The SBF2 c.3290C>A; p.Thr1097Asn variant (rs141894081) is reported in the literature in two individuals undergoing CMT testing (Volodarsky 2021); however, the variant was not determined to be causative. The variant is reported in the ClinVar database (Variation ID: 246062) and is listed in the Latino population with an allele frequency of 0.35% (124/35,440 alleles) in the Genome Aggregation Database. The threonine at codon 1097 is highly conserved but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.198). While the high population frequency suggests that this is likely a benign variant, given the lack of clinical and functional data, the significance of the p.Thr1097Asn variant is uncertain at this time. REFERENCES Volodarsky M et al. Comprehensive genetic sequence and copy number analysis for Charcot-Marie-Tooth disease in a Canadian cohort of 2517 patients. J Med Genet. 2021 Apr;58(4):284-288. PMID: 32376792.

#	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 25, 2025

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