NM_004006.3(DMD):c.6319C>T (p.Arg2107Trp) AND Duchenne muscular dystrophy

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jul 6, 2022
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:: RCV001509576.5

Allele description [Variation Report for NM_004006.3(DMD):c.6319C>T (p.Arg2107Trp)]

NM_004006.3(DMD):c.6319C>T (p.Arg2107Trp)

Gene:

DMD:dystrophin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xp21.1

Genomic location:

Preferred name:

NM_004006.3(DMD):c.6319C>T (p.Arg2107Trp)

HGVS:

NC_000023.11:g.32217035G>A
NG_012232.1:g.1127575C>T
NM_000109.4:c.6295C>T
NM_004006.3:c.6319C>TMANE SELECT
NM_004009.3:c.6307C>T
NM_004010.3:c.5950C>T
NM_004011.4:c.2296C>T
NM_004012.4:c.2287C>T
NP_000100.3:p.Arg2099Trp
NP_003997.1:p.Arg2107Trp
NP_003997.2:p.Arg2107Trp
NP_004000.1:p.Arg2103Trp
NP_004001.1:p.Arg1984Trp
NP_004002.3:p.Arg766Trp
NP_004003.2:p.Arg763Trp
LRG_199t1:c.6319C>T
LRG_199:g.1127575C>T
LRG_199p1:p.Arg2107Trp
NC_000023.10:g.32235152G>A
NM_004006.2:c.6319C>T

Protein change:

R1984W

Links:

dbSNP: rs770711808

NCBI 1000 Genomes Browser:

rs770711808

Molecular consequence:

NM_000109.4:c.6295C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004006.3:c.6319C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004009.3:c.6307C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004010.3:c.5950C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004011.4:c.2296C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004012.4:c.2287C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Duchenne muscular dystrophy (DMD)
Synonyms:: Muscular dystrophy, pseudohypertrophic progressive, Duchenne type
Identifiers:: MONDO: MONDO:0010679; MedGen: C0013264; Orphanet: 98896; OMIM: 310200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001716370	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (May 18, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002205592	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 6, 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

SCV001716370

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(May 18, 2021)

germline

clinical testing

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

SCV002205592

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 6, 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
not provided	germline	no	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

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

Details of each submission

From Genome-Nilou Lab, SCV001716370.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002205592.2

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

Description

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 2107 of the DMD protein (p.Arg2107Trp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with DMD-related conditions. ClinVar contains an entry for this variant (Variation ID: 518680). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). 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

Last Updated: Nov 10, 2024

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