Variant 13-98809432-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_001366683.2(DOCK9):c.5287G>T(p.Ala1763Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,612,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

DOCK9
NM_001366683.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.57

Variant links:

Genes affected

DOCK9 (HGNC:14132): (dedicator of cytokinesis 9) Enables cadherin binding activity. Predicted to be involved in positive regulation of GTPase activity. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

DOCK9 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant where missense usually causes diseases, DOCK9

BP4

Computational evidence support a benign effect (MetaRNN=0.14410678).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK9	NM_001366683.2 linkuse as main transcript	c.5287G>T	p.Ala1763Ser	missense_variant	47/53	ENST00000682017.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK9	ENST00000682017.1 linkuse as main transcript	c.5287G>T	p.Ala1763Ser	missense_variant	47/53		NM_001366683.2	P3

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000971

AC:

AN:

247248

Hom.:

AF XY:

0.0000522

AC XY:

AN XY:

134142

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000643

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:

0.00000891

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000185

AC:

AN:

1460072

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726296

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000608

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152050

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000680

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.000107

AC:

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

Dec 03, 2021

The c.5290G>T (p.A1764S) alteration is located in exon 48 (coding exon 48) of the DOCK9 gene. This alteration results from a G to T substitution at nucleotide position 5290, causing the alanine (A) at amino acid position 1764 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.31

Cadd

Pathogenic

Dann

Uncertain

1.0

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

D;D;D;D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.14

T;T;T;T;T

MetaSVM

Benign

-0.83

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.83

Polyphen

0.34, 0.045

.;B;.;.;B

Vest4

0.82, 0.79

MVP

0.39

MPC

0.97

ClinPred

0.18

GERP RS

5.8

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over