rs2006791

Variant names:

• chr4-3485510-A-G
• rs2006791
• ENST00000513995.1:n.162A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-3485510-A-G
• chr4-3485510-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000513995.1(DOK7):​n.162A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 1,549,968 control chromosomes in the GnomAD database, including 405,822 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (41746 hom., cov: 33)
  • Exomes 𝑓: 0.72 (364076 hom.)
• Consequence: DOK7 ENST00000513995.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.339
• Publications: 12 publications found

Genes affected

DOK7 (HGNC:26594): (docking protein 7) The protein encoded by this gene is essential for neuromuscular synaptogenesis. The protein functions in aneural activation of muscle-specific receptor kinase, which is required for postsynaptic differentiation, and in the subsequent clustering of the acetylcholine receptor in myotubes. This protein can also induce autophosphorylation of muscle-specific receptor kinase. Mutations in this gene are a cause of familial limb-girdle myasthenia autosomal recessive, which is also known as congenital myasthenic syndrome type 1B. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

DOK7 Gene-Disease associations (from GenCC):

• congenital myasthenic syndrome 10

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia
• fetal akinesia deformation sequence 3

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• fetal akinesia deformation sequence 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• postsynaptic congenital myasthenic syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 4-3485510-A-G is Benign according to our data. Variant chr4-3485510-A-G is described in ClinVar as Benign. ClinVar VariationId is 262878.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOK7	NM_173660.5	c.533-29A>G		intron_variant	Intron 4 of 6	ENST00000340083.6	NP_775931.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOK7	ENST00000340083.6	c.533-29A>G		intron_variant	Intron 4 of 6	1	NM_173660.5	ENSP00000344432.5

Frequencies

GnomAD3 genomes AF: 0.738 AC: 112131 AN: 152014 Hom.: 41692 Cov.: 33

Gnomad AFR AF: 0.720

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.932

Gnomad SAS AF: 0.815

Gnomad FIN AF: 0.791

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.702

Gnomad OTH AF: 0.744

GnomAD2 exomes AF: 0.765 AC: 168870 AN: 220616 AF XY: 0.761

Gnomad AFR exome AF: 0.728

Gnomad AMR exome AF: 0.858

Gnomad ASJ exome AF: 0.734

Gnomad EAS exome AF: 0.935

Gnomad FIN exome AF: 0.788

Gnomad NFE exome AF: 0.706

Gnomad OTH exome AF: 0.754

GnomAD4 exome AF: 0.719 AC: 1005208 AN: 1397836 Hom.: 364076 Cov.: 59 AF XY: 0.722 AC XY: 498361 AN XY: 690728

African (AFR) AF: 0.727 AC: 22402 AN: 30814

American (AMR) AF: 0.849 AC: 33863 AN: 39864

Ashkenazi Jewish (ASJ) AF: 0.730 AC: 17978 AN: 24616

East Asian (EAS) AF: 0.942 AC: 33710 AN: 35770

South Asian (SAS) AF: 0.813 AC: 63993 AN: 78732

European-Finnish (FIN) AF: 0.784 AC: 40277 AN: 51362

Middle Eastern (MID) AF: 0.778 AC: 4310 AN: 5540

European-Non Finnish (NFE) AF: 0.696 AC: 746946 AN: 1073862

Other (OTH) AF: 0.729 AC: 41729 AN: 57276

GnomAD4 genome AF: 0.738 AC: 112241 AN: 152132 Hom.: 41746 Cov.: 33 AF XY: 0.746 AC XY: 55505 AN XY: 74372

African (AFR) AF: 0.720 AC: 29885 AN: 41500

American (AMR) AF: 0.808 AC: 12366 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.737 AC: 2558 AN: 3470

East Asian (EAS) AF: 0.931 AC: 4806 AN: 5160

South Asian (SAS) AF: 0.816 AC: 3930 AN: 4816

European-Finnish (FIN) AF: 0.791 AC: 8387 AN: 10606

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.702 AC: 47727 AN: 67964

Other (OTH) AF: 0.746 AC: 1573 AN: 2108

Alfa AF: 0.716 Hom.: 7436

Bravo AF: 0.738

Asia WGS AF: 0.861 AC: 2996 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

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PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Congenital myasthenic syndrome 10 Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Fetal akinesia deformation sequence 3 Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	11
DANN	Benign	0.71
PhyloP100		0.34
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2006791; hg19: chr4-3487237;