rs141947707

Variant names:

• chr4-3492904-C-A
• rs141947707
• NM_173660.5:c.918C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-3492904-C-A
• chr4-3492904-C-G
• chr4-3492904-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_173660.5(DOK7):​c.918C>A​(p.Ala306Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,425,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A306A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DOK7 NM_173660.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.569
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• congenital myasthenic syndrome 10

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia
• fetal akinesia deformation sequence 3

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• fetal akinesia deformation sequence 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• postsynaptic congenital myasthenic syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP7: Synonymous conserved (PhyloP=-0.569 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173660.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOK7	NM_173660.5	MANE Select	c.918C>A	p.Ala306Ala	synonymous	Exon 7 of 7	NP_775931.3
	DOK7	NM_001301071.2		c.918C>A	p.Ala306Ala	synonymous	Exon 7 of 10	NP_001288000.1
	DOK7	NM_001363811.2		c.486C>A	p.Ala162Ala	synonymous	Exon 5 of 8	NP_001350740.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOK7	ENST00000340083.6	TSL:1 MANE Select	c.918C>A	p.Ala306Ala	synonymous	Exon 7 of 7	ENSP00000344432.5
	DOK7	ENST00000643608.1		c.486C>A	p.Ala162Ala	synonymous	Exon 5 of 8	ENSP00000495701.1
	DOK7	ENST00000515886.5	TSL:2	c.-13C>A		5_prime_UTR	Exon 4 of 4	ENSP00000492194.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1425988 Hom.: 0 Cov.: 110 AF XY: 0.00000141 AC XY: 1 AN XY: 706774

African (AFR) AF: 0.00 AC: 0 AN: 32718

American (AMR) AF: 0.00 AC: 0 AN: 39726

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25534

East Asian (EAS) AF: 0.0000266 AC: 1 AN: 37534

South Asian (SAS) AF: 0.00 AC: 0 AN: 82516

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46044

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5730

European-Non Finnish (NFE) AF: 9.12e-7 AC: 1 AN: 1097072

Other (OTH) AF: 0.00 AC: 0 AN: 59114

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.89
DANN	Benign	0.66
PhyloP100		-0.57

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

Other links and lift over

dbSNP: rs141947707; hg19: chr4-3494631;