rs141947707

chr4-3492904-C-Gchr4-3492904-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_173660.5(DOK7):c.918C>G(p.Ala306=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000589 in 1,578,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A306A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000058 (0 hom.)
• Consequence: DOK7 NM_173660.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.569

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 Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 4-3492904-C-G is Benign according to our data. Variant chr4-3492904-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1590347.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.569 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOK7	NM_173660.5	c.918C>G	p.Ala306=	synonymous_variant	7/7	ENST00000340083.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOK7	ENST00000340083.6	c.918C>G	p.Ala306=	synonymous_variant	7/7	1	NM_173660.5	P1

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152176 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.0000431 AC: 8 AN: 185582 Hom.: 0 AF XY: 0.0000395 AC XY: 4 AN XY: 101150

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000353

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000575 AC: 82 AN: 1425988 Hom.: 0 Cov.: 110 AF XY: 0.0000623 AC XY: 44 AN XY: 706774

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000503

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000720

Gnomad4 OTH exome AF: 0.0000169

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152176 Hom.: 0 Cov.: 34 AF XY: 0.0000538 AC XY: 4 AN XY: 74330

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.000479

Alfa AF: 0.0000718 Hom.: 0

Bravo AF: 0.0000642

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 25, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.93
Dann	Benign	0.50

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: rs141947707; hg19: chr4-3494631;