rs772608037

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001367561.1(DOCK7):​c.5172G>C​(p.Met1724Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,768 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

DOCK7
NM_001367561.1 missense

Scores

6
9
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.91

Publications

1 publications found
Variant links:
Genes affected
DOCK7 (HGNC:19190): (dedicator of cytokinesis 7) The protein encoded by this gene is a guanine nucleotide exchange factor (GEF) that plays a role in axon formation and neuronal polarization. The encoded protein displays GEF activity toward RAC1 and RAC3 Rho small GTPases but not toward CDC42. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]
DOCK7 Gene-Disease associations (from GenCC):
  • genetic developmental and epileptic encephalopathy
    Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
  • developmental and epileptic encephalopathy, 23
    Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, G2P

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DOCK7NM_001367561.1 linkc.5172G>C p.Met1724Ile missense_variant Exon 40 of 50 ENST00000635253.2 NP_001354490.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DOCK7ENST00000635253.2 linkc.5172G>C p.Met1724Ile missense_variant Exon 40 of 50 5 NM_001367561.1 ENSP00000489124.1 Q96N67-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00000400
AC:
1
AN:
250088
AF XY:
0.00000740
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000882
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.87e-7
AC:
1
AN:
1454768
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
722814
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33378
American (AMR)
AF:
0.00
AC:
0
AN:
44540
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25998
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39522
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85460
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53304
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5744
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1106766
Other (OTH)
AF:
0.0000167
AC:
1
AN:
60056
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.94
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.030
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.097
.;.;.;T;.;.;T
Eigen
Uncertain
0.67
Eigen_PC
Pathogenic
0.72
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.96
D;D;D;D;D;D;D
M_CAP
Benign
0.058
D
MetaRNN
Uncertain
0.58
D;D;D;D;D;D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Pathogenic
3.0
.;.;.;.;.;.;M
PhyloP100
7.9
PrimateAI
Pathogenic
0.86
D
PROVEAN
Uncertain
-2.4
N;.;N;.;.;.;.
REVEL
Uncertain
0.39
Sift
Uncertain
0.0040
D;.;D;.;.;.;.
Sift4G
Uncertain
0.0090
D;D;D;.;D;D;D
Polyphen
0.78
P;P;B;.;P;B;P
Vest4
0.65
MutPred
0.41
.;.;.;.;.;.;Gain of ubiquitination at K1729 (P = 0.1062);
MVP
0.72
MPC
0.60
ClinPred
0.83
D
GERP RS
6.0
Varity_R
0.49
gMVP
0.63
Mutation Taster
=36/64
disease causing

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

Other links and lift over

dbSNP: rs772608037; hg19: chr1-62959991; API