rs200487431

chr4-3476560-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS1

The NM_173660.5(DOK7):c.532+18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00125 in 1,613,602 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0015 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0012 (5 hom.)
• Consequence: DOK7 NM_173660.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.774

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]

LOC105374355 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 4-3476560-G-A is Benign according to our data. Variant chr4-3476560-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 262877.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00148 (225/152326) while in subpopulation AMR AF= 0.00372 (57/15310). AF 95% confidence interval is 0.00295. There are 1 homozygotes in gnomad4. There are 126 alleles in male gnomad4 subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOK7	NM_173660.5	c.532+18G>A		intron_variant		ENST00000340083.6
LOC105374355	XR_007057994.1	n.606C>T		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOK7	ENST00000340083.6	c.532+18G>A		intron_variant		1	NM_173660.5	P1

Frequencies

GnomAD3 genomes AF: 0.00148 AC: 225 AN: 152208 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000458

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00373

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00423

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00144

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00116 AC: 290 AN: 249394 Hom.: 0 AF XY: 0.00118 AC XY: 159 AN XY: 135246

Gnomad AFR exome AF: 0.000311

Gnomad AMR exome AF: 0.00202

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00336

Gnomad NFE exome AF: 0.00121

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.00122 AC: 1788 AN: 1461276 Hom.: 5 Cov.: 39 AF XY: 0.00118 AC XY: 861 AN XY: 726908

Gnomad4 AFR exome AF: 0.000299

Gnomad4 AMR exome AF: 0.00212

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00304

Gnomad4 NFE exome AF: 0.00128

Gnomad4 OTH exome AF: 0.00162

GnomAD4 genome AF: 0.00148 AC: 225 AN: 152326 Hom.: 1 Cov.: 31 AF XY: 0.00169 AC XY: 126 AN XY: 74490

Gnomad4 AFR AF: 0.000457

Gnomad4 AMR AF: 0.00372

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00423

Gnomad4 NFE AF: 0.00144

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00186 Hom.: 0

Bravo AF: 0.00158

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

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- -

Fetal akinesia deformation sequence 1;C1850792:Congenital myasthenic syndrome 10 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 28, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	8.5
Dann	Benign	0.81

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: rs200487431; hg19: chr4-3478287;