NM_015295.3(SMCHD1):c.3182T>A (p.Ile1061Lys) AND Facioscapulohumeral muscular dystrophy 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 25, 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:: RCV001887253.3

Allele description [Variation Report for NM_015295.3(SMCHD1):c.3182T>A (p.Ile1061Lys)]

NM_015295.3(SMCHD1):c.3182T>A (p.Ile1061Lys)

Gene:

SMCHD1:structural maintenance of chromosomes flexible hinge domain containing 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

18p11.32

Genomic location:

Preferred name:

NM_015295.3(SMCHD1):c.3182T>A (p.Ile1061Lys)

HGVS:

NC_000018.10:g.2732398T>A
NG_031972.1:g.81511T>A
NM_015295.3:c.3182T>AMANE SELECT
NP_056110.2:p.Ile1061Lys
NC_000018.9:g.2732396T>A

Protein change:

I1061K

Links:

dbSNP: rs764839018

NCBI 1000 Genomes Browser:

rs764839018

Molecular consequence:

NM_015295.3:c.3182T>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Facioscapulohumeral muscular dystrophy 2 (FSHD2)
Synonyms:: MUSCULAR DYSTROPHY, FACIOSCAPULOHUMERAL, TYPE 1B; FACIOSCAPULOHUMERAL MUSCULAR DYSTROPHY 2, DIGENIC; FSHD2, DIGENIC
Identifiers:: MONDO: MONDO:0008031; MedGen: C1834671; Orphanet: 269; OMIM: 158901

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002165584	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 25, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002165584

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 25, 2022)

germline

clinical testing

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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 Invitae, SCV002165584.3

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

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1395766). This variant has not been reported in the literature in individuals affected with SMCHD1-related conditions. This variant is present in population databases (rs764839018, gnomAD 0.006%). This sequence change replaces isoleucine, which is neutral and non-polar, with lysine, which is basic and polar, at codon 1061 of the SMCHD1 protein (p.Ile1061Lys).

#	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: Feb 20, 2024

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