NM_173660.5(DOK7):c.577A>G (p.Ser193Gly) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 1, 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:: RCV000700198.5

Allele description [Variation Report for NM_173660.5(DOK7):c.577A>G (p.Ser193Gly)]

NM_173660.5(DOK7):c.577A>G (p.Ser193Gly)

Genes:

LOC126806951:CDK7 strongly-dependent group 2 enhancer GRCh37_chr4:3486115-3487314 [Gene]
DOK7:docking protein 7 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4p16.3

Genomic location:

Preferred name:

NM_173660.5(DOK7):c.577A>G (p.Ser193Gly)

Other names:

p.Ser193Gly

HGVS:

NC_000004.12:g.3485583A>G
NG_013072.2:g.27278A>G
NM_001164673.2:c.566A>G
NM_001256896.2:c.-354A>G
NM_001301071.2:c.577A>G
NM_001363811.2:c.145A>G
NM_173660.5:c.577A>GMANE SELECT
NP_001158145.1:p.Gln189Arg
NP_001288000.1:p.Ser193Gly
NP_001350740.1:p.Ser49Gly
NP_775931.3:p.Ser193Gly
LRG_869t1:c.577A>G
LRG_869:g.27278A>G
LRG_869p1:p.Ser193Gly
NC_000004.11:g.3487310A>G
NM_173660.4:c.577A>G

Protein change:

Q189R

Links:

dbSNP: rs139133047

NCBI 1000 Genomes Browser:

rs139133047

Molecular consequence:

NM_001256896.2:c.-354A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001164673.2:c.566A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001301071.2:c.577A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001363811.2:c.145A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_173660.5:c.577A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Fetal akinesia deformation sequence 1 (FADS1)
Synonyms:: Pena Shokeir syndrome, type 1; Lethal Pena-Shokeir 1 syndrome; Pena-Shokeir syndrome type I; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0100101; MedGen: C1276035; Orphanet: 994; OMIM: 208150; Human Phenotype Ontology: HP:0001989

Name:: Congenital myasthenic syndrome 10
Synonyms:: Myasthenia, limb-girdle, familial
Identifiers:: MONDO: MONDO:0009690; MedGen: C1850792; Orphanet: 590; OMIM: 254300

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000828945	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 1, 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

SCV000828945

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 1, 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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000828945.5

#	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 serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 193 of the DOK7 protein (p.Ser193Gly). This variant is present in population databases (rs139133047, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with DOK7-related conditions. ClinVar contains an entry for this variant (Variation ID: 418166). 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: "Probably 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: May 7, 2024

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