rs17709314

chr13-98826885-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001366683.2(DOCK9):c.4968A>G(p.Ala1656=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,605,618 control chromosomes in the GnomAD database, including 9,619 homozygotes. 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 0.077 (571 hom., cov: 33)
  • Exomes 𝑓: 0.11 (9048 hom.)
• Consequence: DOCK9 NM_001366683.2 splice_region, synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.687

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP7: Synonymous conserved (PhyloP=-0.687 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK9	NM_001366683.2	c.4968A>G	p.Ala1656=	splice_region_variant, synonymous_variant	44/53	ENST00000682017.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK9	ENST00000682017.1	c.4968A>G	p.Ala1656=	splice_region_variant, synonymous_variant	44/53		NM_001366683.2	P3

Frequencies

GnomAD3 genomes AF: 0.0767 AC: 11673 AN: 152202 Hom.: 570 Cov.: 33

Gnomad AFR AF: 0.0218

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.0683

Gnomad ASJ AF: 0.0790

Gnomad EAS AF: 0.000960

Gnomad SAS AF: 0.0553

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.0789

GnomAD3 exomes AF: 0.0799 AC: 19302 AN: 241662 Hom.: 962 AF XY: 0.0815 AC XY: 10648 AN XY: 130708

Gnomad AFR exome AF: 0.0209

Gnomad AMR exome AF: 0.0408

Gnomad ASJ exome AF: 0.0753

Gnomad EAS exome AF: 0.000398

Gnomad SAS exome AF: 0.0583

Gnomad FIN exome AF: 0.113

Gnomad NFE exome AF: 0.112

Gnomad OTH exome AF: 0.0876

GnomAD4 exome AF: 0.106 AC: 153632 AN: 1453298 Hom.: 9048 Cov.: 29 AF XY: 0.105 AC XY: 75646 AN XY: 722552

Gnomad4 AFR exome AF: 0.0194

Gnomad4 AMR exome AF: 0.0436

Gnomad4 ASJ exome AF: 0.0778

Gnomad4 EAS exome AF: 0.000404

Gnomad4 SAS exome AF: 0.0589

Gnomad4 FIN exome AF: 0.118

Gnomad4 NFE exome AF: 0.119

Gnomad4 OTH exome AF: 0.0960

GnomAD4 genome AF: 0.0766 AC: 11675 AN: 152320 Hom.: 571 Cov.: 33 AF XY: 0.0750 AC XY: 5584 AN XY: 74488

Gnomad4 AFR AF: 0.0217

Gnomad4 AMR AF: 0.0682

Gnomad4 ASJ AF: 0.0790

Gnomad4 EAS AF: 0.000963

Gnomad4 SAS AF: 0.0556

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.0781

Alfa AF: 0.102 Hom.: 1147

Bravo AF: 0.0706

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	4.2
Dann	Benign	0.71

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: rs17709314; hg19: chr13-99479139;