rs9517459

chr13-98829776-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001366683.2(DOCK9):c.4636-20C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 1,573,730 control chromosomes in the GnomAD database, including 40,015 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 0.21 (3576 hom., cov: 32)
  • Exomes 𝑓: 0.22 (36439 hom.)
• Consequence: DOCK9 NM_001366683.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.532

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK9	NM_001366683.2	c.4636-20C>G		intron_variant		ENST00000682017.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK9	ENST00000682017.1	c.4636-20C>G		intron_variant			NM_001366683.2	P3

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31422 AN: 152004 Hom.: 3569 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.186

GnomAD3 exomes AF: 0.211 AC: 41977 AN: 199348 Hom.: 5120 AF XY: 0.209 AC XY: 22248 AN XY: 106256

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.107

Gnomad ASJ exome AF: 0.206

Gnomad EAS exome AF: 0.443

Gnomad SAS exome AF: 0.106

Gnomad FIN exome AF: 0.243

Gnomad NFE exome AF: 0.235

Gnomad OTH exome AF: 0.211

GnomAD4 exome AF: 0.220 AC: 313354 AN: 1421606 Hom.: 36439 Cov.: 28 AF XY: 0.218 AC XY: 153662 AN XY: 704310

Gnomad4 AFR exome AF: 0.161

Gnomad4 AMR exome AF: 0.107

Gnomad4 ASJ exome AF: 0.200

Gnomad4 EAS exome AF: 0.349

Gnomad4 SAS exome AF: 0.107

Gnomad4 FIN exome AF: 0.241

Gnomad4 NFE exome AF: 0.231

Gnomad4 OTH exome AF: 0.214

GnomAD4 genome AF: 0.207 AC: 31470 AN: 152124 Hom.: 3576 Cov.: 32 AF XY: 0.206 AC XY: 15296 AN XY: 74372

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.197

Gnomad4 EAS AF: 0.423

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.233

Gnomad4 OTH AF: 0.186

Alfa AF: 0.218 Hom.: 718

Bravo AF: 0.197

Asia WGS AF: 0.220 AC: 769 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	3.9
Dann	Benign	0.58

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: rs9517459; hg19: chr13-99482030; COSMIC: COSV59622264; COSMIC: COSV59622264;