Genetic Variant DOK7:c.331+43G>T (chr4-3473679-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_173660.5(DOK7):c.331+43G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.032 in 1,499,750 control chromosomes in the GnomAD database, including 1,352 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.055 ( 401 hom., cov: 33)

Exomes 𝑓: 0.029 ( 951 hom. )

Consequence

DOK7
NM_173660.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.82

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 4-3473679-G-T is Benign according to our data. Variant chr4-3473679-G-T is described in ClinVar as [Benign]. Clinvar id is 262874.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOK7	NM_173660.5 link	c.331+43G>T		intron_variant	Intron 3 of 6	ENST00000340083.6	NP_775931.3	Q18PE1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOK7	ENST00000340083.6 link	c.331+43G>T		intron_variant	Intron 3 of 6	1	NM_173660.5	ENSP00000344432.5		Q18PE1-1

Frequencies

GnomAD3 genomes

AF:

0.0552

AC:

8410

AN:

152224

Hom.:

401

Cov.:

show subpopulations

Gnomad AFR

AF:

0.116

Gnomad AMI

AF:

0.00330

Gnomad AMR

AF:

0.0706

Gnomad ASJ

AF:

0.0386

Gnomad EAS

AF:

0.0717

Gnomad SAS

AF:

0.0573

Gnomad FIN

AF:

0.00941

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0222

Gnomad OTH

AF:

0.0430

GnomAD3 exomes

AF:

0.0515

AC:

6284

AN:

122072

Hom.:

265

AF XY:

0.0492

AC XY:

3140

AN XY:

63758

show subpopulations

Gnomad AFR exome

AF:

0.116

Gnomad AMR exome

AF:

0.102

Gnomad ASJ exome

AF:

0.0416

Gnomad EAS exome

AF:

0.0640

Gnomad SAS exome

AF:

0.0577

Gnomad FIN exome

AF:

0.00737

Gnomad NFE exome

AF:

0.0234

Gnomad OTH exome

AF:

0.0496

GnomAD4 exome

AF:

0.0294

AC:

39550

AN:

1347408

Hom.:

951

Cov.:

AF XY:

0.0295

AC XY:

19372

AN XY:

656754

show subpopulations

Gnomad4 AFR exome

AF:

0.113

Gnomad4 AMR exome

AF:

0.0969

Gnomad4 ASJ exome

AF:

0.0370

Gnomad4 EAS exome

AF:

0.0756

Gnomad4 SAS exome

AF:

0.0564

Gnomad4 FIN exome

AF:

0.00897

Gnomad4 NFE exome

AF:

0.0215

Gnomad4 OTH exome

AF:

0.0363

GnomAD4 genome

AF:

0.0553

AC:

8420

AN:

152342

Hom.:

401

Cov.:

AF XY:

0.0542

AC XY:

4036

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.116

Gnomad4 AMR

AF:

0.0710

Gnomad4 ASJ

AF:

0.0386

Gnomad4 EAS

AF:

0.0720

Gnomad4 SAS

AF:

0.0563

Gnomad4 FIN

AF:

0.00941

Gnomad4 NFE

AF:

0.0222

Gnomad4 OTH

AF:

0.0426

Alfa

AF:

0.0382

Hom.:

Bravo

AF:

0.0619

Asia WGS

AF:

0.0790

AC:

275

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 06, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

-0.93

CADD

Benign

0.60

DANN

Benign

0.66

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over