NM_004393.6(DAG1):c.175G>T (p.Glu59Ter) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 3, 2021
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:: RCV001855933.3

Allele description [Variation Report for NM_004393.6(DAG1):c.175G>T (p.Glu59Ter)]

NM_004393.6(DAG1):c.175G>T (p.Glu59Ter)

Gene:

DAG1:dystroglycan 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p21.31

Genomic location:

Preferred name:

NM_004393.6(DAG1):c.175G>T (p.Glu59Ter)

HGVS:

NC_000003.12:g.49510709G>T
NG_013230.4:g.45578G>T
NM_001165928.4:c.175G>T
NM_001177634.3:c.175G>T
NM_001177635.3:c.175G>T
NM_001177636.3:c.175G>T
NM_001177637.3:c.175G>T
NM_001177638.3:c.175G>T
NM_001177639.3:c.175G>T
NM_001177640.3:c.175G>T
NM_001177641.3:c.175G>T
NM_001177642.3:c.175G>T
NM_001177643.3:c.175G>T
NM_001177644.3:c.175G>T
NM_004393.6:c.175G>TMANE SELECT
NP_001159400.3:p.Glu59Ter
NP_001171105.2:p.Glu59Ter
NP_001171106.2:p.Glu59Ter
NP_001171107.2:p.Glu59Ter
NP_001171108.2:p.Glu59Ter
NP_001171109.2:p.Glu59Ter
NP_001171110.2:p.Glu59Ter
NP_001171111.2:p.Glu59Ter
NP_001171112.2:p.Glu59Ter
NP_001171113.2:p.Glu59Ter
NP_001171114.2:p.Glu59Ter
NP_001171115.2:p.Glu59Ter
NP_004384.4:p.Glu59Ter
NP_004384.5:p.Glu59Ter
LRG_854t1:c.175G>T
LRG_854t2:c.175G>T
LRG_854:g.45578G>T
LRG_854p1:p.Glu59Ter
LRG_854p2:p.Glu59Ter
NC_000003.11:g.49548142G>T
NM_004393.5:c.175G>T

Protein change:

E59*

Links:

dbSNP: rs767737417

NCBI 1000 Genomes Browser:

rs767737417

Molecular consequence:

NM_001165928.4:c.175G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001177634.3:c.175G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001177635.3:c.175G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001177636.3:c.175G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001177637.3:c.175G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001177638.3:c.175G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001177639.3:c.175G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001177640.3:c.175G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001177641.3:c.175G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001177642.3:c.175G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001177643.3:c.175G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001177644.3:c.175G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_004393.6:c.175G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Autosomal recessive limb-girdle muscular dystrophy type 2P
Synonyms:: MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY, LIMB-GIRDLE, DAG1-RELATED; Limb-girdle muscular dystrophy-dystroglycanopathy, type C9; MUSCULAR DYSTROPHY, LIMB-GIRDLE, TYPE 2P; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0013440; MedGen: C4511963; Orphanet: 280333; OMIM: 613818

Name:: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9
Synonyms:: WALKER-WARBURG SYNDROME OR MUSCLE-EYE BRAIN DISEASE, DAG1-RELATED; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 9
Identifiers:: MONDO: MONDO:0014683; MedGen: C4225291; Orphanet: 370997; Orphanet: 899; OMIM: 616538

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002309216	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 3, 2021)	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

SCV002309216

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 3, 2021)

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV002309216.3

#	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 creates a premature translational stop signal (p.Glu59*) in the DAG1 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in DAG1 cause disease. This variant is not present in population databases (ExAC no frequency). 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. ClinVar contains an entry for this variant (Variation ID: 620516). This variant has not been reported in the literature in individuals affected with DAG1-related conditions.

#	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 28, 2024

ClinVar

Relating variation to medicine