rs773679215

Positions:

• chr4-3493464-C-A
• chr4-3493464-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_173660.5(DOK7):​c.1478C>A​(p.Pro493Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DOK7 NM_173660.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.42

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOK7	NM_173660.5	c.1478C>A	p.Pro493Gln	missense_variant	7/7	ENST00000340083.6	NP_775931.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOK7	ENST00000340083.6	c.1478C>A	p.Pro493Gln	missense_variant	7/7	1	NM_173660.5	ENSP00000344432.5
DOK7	ENST00000643608.1	c.1046C>A	p.Pro349Gln	missense_variant	5/8			ENSP00000495701.1
DOK7	ENST00000515886.5	c.548C>A	p.Pro183Gln	missense_variant	4/4	2		ENSP00000492194.1
DOK7	ENST00000507039.5	c.*699C>A		3_prime_UTR_variant	7/7	2		ENSP00000423614.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1458434 Hom.: 0 Cov.: 87 AF XY: 0.00 AC XY: 0 AN XY: 725356

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.53	D;.;.
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.64	D;D;D
MetaSVM	Uncertain	0.16	D
MutationAssessor	Uncertain	2.1	M;.;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-4.0	D;.;.
REVEL	Benign	0.27
Sift	Uncertain	0.0030	D;.;.
Sift4G	Uncertain	0.0020	D;.;.
Polyphen		0.89	P;.;.
Vest4		0.50
MVP		0.83
MPC		0.012
ClinPred		0.98	D
GERP RS		3.8
Varity_R		0.36
gMVP		0.23

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: rs773679215; hg19: chr4-3495191;