13-98824401-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001366683.2(DOCK9):c.5127C>T(p.Asn1709=) 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0500

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]

ACMG classification

Verdict is Benign. Variant got -9 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_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.05 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK9	NM_001366683.2	c.5127C>T	p.Asn1709=	synonymous_variant	45/53	ENST00000682017.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK9	ENST00000682017.1	c.5127C>T	p.Asn1709=	synonymous_variant	45/53		NM_001366683.2	P3

Frequencies

GnomAD3 genomes AF: 0.00221 AC: 336 AN: 152222 Hom.: 0 Cov.: 32

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.: 5 AF XY: 0.00269 AC XY: 363 AN XY: 135126

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.: 15 Cov.: 30 AF XY: 0.00277 AC XY: 2012 AN XY: 726956

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.: 0 Cov.: 32 AF XY: 0.00199 AC XY: 148 AN XY: 74490

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.: 2

Bravo AF: 0.00234

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00414

EpiControl AF: 0.00338

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 03, 2018

- -

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

Other links and lift over

dbSNP: rs11617965; hg19: chr13-99476655;