chr8-25296564-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_024940.8(DOCK5):​c.522C>T​(p.Asp174Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000475 in 1,612,094 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.

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00048 ( 0 hom. )

Consequence

DOCK5
NM_024940.8 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0730
Variant links:
Genes affected
DOCK5 (HGNC:23476): (dedicator of cytokinesis 5) This gene encodes a member of the dedicator of cytokinesis protein family. Members of this family act as guanine nucleotide exchange factors for small Rho family G proteins. The protein encoded by this gene is thought to associate with adaptors CRK and CRKL, and function in regulation of intestinal epithelial cell spreading and migration on collagen IV. Similar proteins in mouse and zebrafish also function in myoblast fusion. [provided by RefSeq, Oct 2016]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP7
Synonymous conserved (PhyloP=0.073 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DOCK5NM_024940.8 linkc.522C>T p.Asp174Asp synonymous_variant Exon 7 of 52 ENST00000276440.12 NP_079216.4 Q9H7D0-1Q68DL4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DOCK5ENST00000276440.12 linkc.522C>T p.Asp174Asp synonymous_variant Exon 7 of 52 1 NM_024940.8 ENSP00000276440.7 Q9H7D0-1
DOCK5ENST00000481100.5 linkc.522C>T p.Asp174Asp synonymous_variant Exon 7 of 11 1 ENSP00000429737.1 Q9H7D0-2
DOCK5ENST00000495236.1 linkn.-18C>T upstream_gene_variant 4

Frequencies

GnomAD3 genomes
AF:
0.000395
AC:
60
AN:
152080
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00105
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000544
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.000214
AC:
53
AN:
247678
Hom.:
0
AF XY:
0.000164
AC XY:
22
AN XY:
133822
show subpopulations
Gnomad AFR exome
AF:
0.0000630
Gnomad AMR exome
AF:
0.000263
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000376
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.000483
AC:
705
AN:
1460014
Hom.:
0
Cov.:
30
AF XY:
0.000460
AC XY:
334
AN XY:
726090
show subpopulations
Gnomad4 AFR exome
AF:
0.0000897
Gnomad4 AMR exome
AF:
0.000270
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:
0.000589
Gnomad4 OTH exome
AF:
0.000580
GnomAD4 genome
AF:
0.000395
AC:
60
AN:
152080
Hom.:
0
Cov.:
32
AF XY:
0.000471
AC XY:
35
AN XY:
74292
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.00105
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000544
Gnomad4 OTH
AF:
0.00191
Alfa
AF:
0.000245
Hom.:
0
Bravo
AF:
0.000427

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.46
CADD
Benign
5.2
DANN
Benign
0.37
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs150049709; hg19: chr8-25154080; API