rs566267525

chr4-3463582-CG-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_173660.5(DOK7):c.100+36del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0045 in 1,016,136 control chromosomes in the GnomAD database, including 154 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (81 hom., cov: 33)
  • Exomes 𝑓: 0.0023 (73 hom.)
• Consequence: DOK7 NM_173660.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.429

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 4-3463582-CG-C is Benign according to our data. Variant chr4-3463582-CG-C is described in ClinVar as [Likely_benign]. Clinvar id is 262862.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOK7	NM_173660.5	c.100+36del		intron_variant		ENST00000340083.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOK7	ENST00000340083.6	c.100+36del		intron_variant		1	NM_173660.5	P1

Frequencies

GnomAD3 genomes AF: 0.0173 AC: 2529 AN: 146210 Hom.: 80 Cov.: 33

Gnomad AFR AF: 0.0612

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00602

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000220

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00329

Gnomad NFE AF: 0.0000905

Gnomad OTH AF: 0.00890

GnomAD3 exomes AF: 0.00325 AC: 412 AN: 126770 Hom.: 7 AF XY: 0.00236 AC XY: 164 AN XY: 69528

Gnomad AFR exome AF: 0.0613

Gnomad AMR exome AF: 0.00207

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000136

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000211

Gnomad OTH exome AF: 0.00254

GnomAD4 exome AF: 0.00234 AC: 2036 AN: 869844 Hom.: 73 Cov.: 31 AF XY: 0.00187 AC XY: 829 AN XY: 442616

Gnomad4 AFR exome AF: 0.0800

Gnomad4 AMR exome AF: 0.00304

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000158

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000360

Gnomad4 OTH exome AF: 0.00484

GnomAD4 genome AF: 0.0173 AC: 2538 AN: 146292 Hom.: 81 Cov.: 33 AF XY: 0.0165 AC XY: 1180 AN XY: 71430

Gnomad4 AFR AF: 0.0612

Gnomad4 AMR AF: 0.00601

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000221

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000905

Gnomad4 OTH AF: 0.00881

Alfa AF: 0.00902 Hom.: 3

Bravo AF: 0.0205

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs566267525; hg19: chr4-3465309;