Genetic Variant DOCK9:p.Asn1709Asn (chr13-98824401-G-A) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_001366683.2(DOCK9):c.5127C>T(p.Asn1709Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00274 in 1,613,662 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 15 hom. )

Consequence

DOCK9
NM_001366683.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0500

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 13-98824401-G-A is Benign according to our data. Variant chr13-98824401-G-A is described in ClinVar as [Benign]. Clinvar id is 781704.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.05 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 15 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK9	NM_001366683.2 link	c.5127C>T	p.Asn1709Asn	synonymous_variant	Exon 45 of 53	ENST00000682017.1	NP_001353612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK9	ENST00000682017.1 link	c.5127C>T	p.Asn1709Asn	synonymous_variant	Exon 45 of 53		NM_001366683.2	ENSP00000507034.1		A0A804HIE8

Frequencies

GnomAD3 genomes

AF:

0.00221

AC:

336

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00893

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00226

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00306

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00269

AC:

669

AN:

248984

Hom.:

AF XY:

0.00269

AC XY:

363

AN XY:

135126

show subpopulations

Gnomad AFR exome

AF:

0.000710

Gnomad AMR exome

AF:

0.00235

Gnomad ASJ exome

AF:

0.00805

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00252

Gnomad FIN exome

AF:

0.00246

Gnomad NFE exome

AF:

0.00302

Gnomad OTH exome

AF:

0.00397

GnomAD4 exome

AF:

0.00279

AC:

4081

AN:

1461322

Hom.:

Cov.:

AF XY:

0.00277

AC XY:

2012

AN XY:

726956

show subpopulations

Gnomad4 AFR exome

AF:

0.00117

Gnomad4 AMR exome

AF:

0.00237

Gnomad4 ASJ exome

AF:

0.00922

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00231

Gnomad4 FIN exome

AF:

0.00236

Gnomad4 NFE exome

AF:

0.00278

Gnomad4 OTH exome

AF:

0.00388

GnomAD4 genome

AF:

0.00222

AC:

338

AN:

152340

Hom.:

Cov.:

AF XY:

0.00199

AC XY:

148

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000673

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00893

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00226

Gnomad4 NFE

AF:

0.00306

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00297

Hom.:

Bravo

AF:

0.00234

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00414

EpiControl

AF:

0.00338

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 03, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

3.6

DANN

Benign

0.79

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.

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