chr18-69677794-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_152721.6(DOK6):c.350A>G(p.Asn117Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000234 in 1,613,782 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00025 ( 0 hom. )
Consequence
DOK6
NM_152721.6 missense
NM_152721.6 missense
Scores
2
4
13
Clinical Significance
Conservation
PhyloP100: 9.25
Genes affected
DOK6 (HGNC:28301): (docking protein 6) DOK6 is a member of the DOK (see DOK1; MIM 602919) family of intracellular adaptors that play a role in the RET (MIM 164761) signaling cascade (Crowder et al., 2004 [PubMed 15286081]).[supplied by OMIM, Mar 2008]
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ACMG classification
Classification made for transcript
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 | UniProt |
---|---|---|---|---|---|---|---|
DOK6 | NM_152721.6 | c.350A>G | p.Asn117Ser | missense_variant | 4/8 | ENST00000382713.10 | |
DOK6 | XM_017025610.2 | c.26A>G | p.Asn9Ser | missense_variant | 2/6 | ||
DOK6 | XM_017025611.2 | c.26A>G | p.Asn9Ser | missense_variant | 2/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOK6 | ENST00000382713.10 | c.350A>G | p.Asn117Ser | missense_variant | 4/8 | 1 | NM_152721.6 | P1 | |
DOK6 | ENST00000582992.1 | c.62A>G | p.Asn21Ser | missense_variant | 1/3 | 3 | |||
DOK6 | ENST00000582172.5 | n.321A>G | non_coding_transcript_exon_variant | 3/4 | 3 | ||||
DOK6 | ENST00000584435.1 | n.164A>G | non_coding_transcript_exon_variant | 2/4 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000125 AC: 19AN: 152180Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000139 AC: 35AN: 251428Hom.: 0 AF XY: 0.000125 AC XY: 17AN XY: 135880
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GnomAD4 exome AF: 0.000246 AC: 359AN: 1461602Hom.: 0 Cov.: 29 AF XY: 0.000241 AC XY: 175AN XY: 727102
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GnomAD4 genome ? AF: 0.000125 AC: 19AN: 152180Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10AN XY: 74352
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 23, 2023 | The c.350A>G (p.N117S) alteration is located in exon 4 (coding exon 4) of the DOK6 gene. This alteration results from a A to G substitution at nucleotide position 350, causing the asparagine (N) at amino acid position 117 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at