NM_173660.5(DOK7):c.1367T>G (p.Met456Arg) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 28, 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:: RCV001352322.6

Allele description [Variation Report for NM_173660.5(DOK7):c.1367T>G (p.Met456Arg)]

NM_173660.5(DOK7):c.1367T>G (p.Met456Arg)

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.1367T>G (p.Met456Arg)

HGVS:

NC_000004.12:g.3493353T>G
NG_013072.2:g.35048T>G
NM_001164673.2:c.*588T>G
NM_001256896.2:c.437T>G
NM_001301071.2:c.1367T>G
NM_001363811.2:c.935T>G
NM_173660.4:c.1367T>G
NM_173660.5:c.1367T>GMANE SELECT
NP_001243825.1:p.Met146Arg
NP_001288000.1:p.Met456Arg
NP_001350740.1:p.Met312Arg
NP_775931.3:p.Met456Arg
LRG_869t1:c.1367T>G
LRG_869:g.35048T>G
LRG_869p1:p.Met456Arg
NC_000004.11:g.3495080T>G

Protein change:

M146R

Links:

dbSNP: rs753317302

NCBI 1000 Genomes Browser:

rs753317302

Molecular consequence:

NM_001164673.2:c.*588T>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001256896.2:c.437T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001301071.2:c.1367T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001363811.2:c.935T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_173660.5:c.1367T>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
SCV001546869	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 28, 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

SCV001546869

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 28, 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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001546869.3

#	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 replaces methionine with arginine at codon 456 of the DOK7 protein (p.Met456Arg). The methionine residue is weakly conserved and there is a moderate physicochemical difference between methionine and arginine. This variant is present in population databases (rs753317302, ExAC 0.003%). This variant has not been reported in the literature in individuals affected with DOK7-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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: Sep 29, 2024

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