NM_024577.4(SH3TC2):c.3733_3734del (p.Leu1244_Gly1245insTer) AND Charcot-Marie-Tooth disease type 4C

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 19, 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:: RCV003108249.2

Allele description [Variation Report for NM_024577.4(SH3TC2):c.3733_3734del (p.Leu1244_Gly1245insTer)]

NM_024577.4(SH3TC2):c.3733_3734del (p.Leu1244_Gly1245insTer)

Gene:

SH3TC2:SH3 domain and tetratricopeptide repeats 2 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

5q32

Genomic location:

Preferred name:

NM_024577.4(SH3TC2):c.3733_3734del (p.Leu1244_Gly1245insTer)

HGVS:

NC_000005.10:g.149004845_149004846del
NG_007947.2:g.63330_63331del
NM_024577.4:c.3733_3734delMANE SELECT
NP_078853.2:p.Leu1244_Gly1245insTer
LRG_269:g.63330_63331del
NC_000005.9:g.148384408_148384409del

Links:

dbSNP: rs2127391399

NCBI 1000 Genomes Browser:

rs2127391399

Molecular consequence:

NM_024577.4:c.3733_3734del - nonsense - [Sequence Ontology: SO:0001587]

Functional consequence:

loss_of_function_variant [Sequence Ontology: SO:0002054]

Condition(s)

Name:: Charcot-Marie-Tooth disease type 4C (CMT4C)
Synonyms:: CHARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, AUTOSOMAL RECESSIVE, TYPE 4C; CMT 4C; Charcot-Marie-Tooth Neuropathy Type 4C (CMT4C); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011113; MedGen: C1866636; Orphanet: 99949; OMIM: 601596

Recent activity

Clear Turn Off Turn On

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
SCV003761519	Pangenia Genomics, Pangenia Inc.	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Oct 19, 2022)	paternal	research

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003761519

Pangenia Genomics, Pangenia Inc.

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Oct 19, 2022)

paternal

research

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
Asian	paternal	yes	1	not provided	not provided	not provided	not provided	research

Details of each submission

From Pangenia Genomics, Pangenia Inc., SCV003761519.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Asian	1	not provided	not provided	research	not provided

Description

The SH3TC2, c.3733_3734del (p.Gly1245Ter) variant creates a premature stop codon within the last exon of gene SH3TC2 for which loss-of-function is a known mechanism of Charcot-Marie-Tooth disease, type 4C. It is not expected to result in nonsense-mediated decay of the transcript, and is expected to remove <10% of the protein while the role of region in protein function is unknown. This variant is absent from the gnomAD v2.1.1 dataset with good coverage of the locus. This variant is detected in trans with a likely-pathogenic variant [SH3TC2, c.2838_2850dup (p.Leu951IlefsTer32)]. Hence, this variant was classified as a VUS (variant of uncertain significance).

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

Last Updated: Dec 24, 2023

ClinVar

Relating variation to medicine