chr18-69841334-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_152721.6(DOK6):c.947C>T(p.Ser316Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000904 in 1,614,154 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00022 ( 1 hom., cov: 33)
Exomes 𝑓: 0.000077 ( 0 hom. )
Consequence
DOK6
NM_152721.6 missense
NM_152721.6 missense
Scores
9
10
Clinical Significance
Conservation
PhyloP100: 5.19
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]
CD226 (HGNC:16961): (CD226 molecule) This gene encodes a glycoprotein expressed on the surface of NK cells, platelets, monocytes and a subset of T cells. It is a member of the Ig-superfamily containing 2 Ig-like domains of the V-set. The protein mediates cellular adhesion of platelets and megakaryocytic cells to vascular endothelial cells. The protein also plays a role in megakaryocytic cell maturation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.06429806).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DOK6 | NM_152721.6 | c.947C>T | p.Ser316Leu | missense_variant | 8/8 | ENST00000382713.10 | |
DOK6 | XM_017025610.2 | c.623C>T | p.Ser208Leu | missense_variant | 6/6 | ||
DOK6 | XM_017025611.2 | c.623C>T | p.Ser208Leu | missense_variant | 6/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOK6 | ENST00000382713.10 | c.947C>T | p.Ser316Leu | missense_variant | 8/8 | 1 | NM_152721.6 | P1 | |
CD226 | ENST00000578928.1 | c.*107+950G>A | intron_variant, NMD_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.000210 AC: 32AN: 152152Hom.: 1 Cov.: 33
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?
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GnomAD3 exomes AF: 0.000131 AC: 33AN: 251452Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135908
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GnomAD4 exome AF: 0.0000773 AC: 113AN: 1461884Hom.: 0 Cov.: 30 AF XY: 0.0000605 AC XY: 44AN XY: 727244
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GnomAD4 genome ? AF: 0.000217 AC: 33AN: 152270Hom.: 1 Cov.: 33 AF XY: 0.000107 AC XY: 8AN XY: 74450
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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 | Mar 31, 2022 | The c.947C>T (p.S316L) alteration is located in exon 8 (coding exon 8) of the DOK6 gene. This alteration results from a C to T substitution at nucleotide position 947, causing the serine (S) at amino acid position 316 to be replaced by a leucine (L). 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
Uncertain
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
P
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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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