rs9554522

chr13-98796187-T-Achr13-98796187-T-G

Variant summary

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

The NM_001366683.2(DOCK9):c.6156+928A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 1,556,216 control chromosomes in the GnomAD database, including 146,905 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 0.42 (13764 hom., cov: 32)
  • Exomes 𝑓: 0.43 (133141 hom.)
• Consequence: DOCK9 NM_001366683.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK9	NM_001366683.2	c.6156+928A>T		intron_variant		ENST00000682017.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK9	ENST00000682017.1	c.6156+928A>T		intron_variant			NM_001366683.2	P3

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63571 AN: 151894 Hom.: 13757 Cov.: 32

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.403

GnomAD3 exomes AF: 0.417 AC: 82593 AN: 197932 Hom.: 18025 AF XY: 0.413 AC XY: 43681 AN XY: 105704

Gnomad AFR exome AF: 0.357

Gnomad AMR exome AF: 0.332

Gnomad ASJ exome AF: 0.397

Gnomad EAS exome AF: 0.636

Gnomad SAS exome AF: 0.298

Gnomad FIN exome AF: 0.488

Gnomad NFE exome AF: 0.440

Gnomad OTH exome AF: 0.402

GnomAD4 exome AF: 0.430 AC: 604375 AN: 1404204 Hom.: 133141 Cov.: 26 AF XY: 0.428 AC XY: 298096 AN XY: 696028

Gnomad4 AFR exome AF: 0.356

Gnomad4 AMR exome AF: 0.328

Gnomad4 ASJ exome AF: 0.388

Gnomad4 EAS exome AF: 0.599

Gnomad4 SAS exome AF: 0.306

Gnomad4 FIN exome AF: 0.488

Gnomad4 NFE exome AF: 0.439

Gnomad4 OTH exome AF: 0.419

GnomAD4 genome AF: 0.418 AC: 63606 AN: 152012 Hom.: 13764 Cov.: 32 AF XY: 0.419 AC XY: 31112 AN XY: 74316

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.622

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.495

Gnomad4 NFE AF: 0.451

Gnomad4 OTH AF: 0.400

Alfa AF: 0.434 Hom.: 2785

Bravo AF: 0.404

Asia WGS AF: 0.420 AC: 1462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	9.3
Dann	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9554522; hg19: chr13-99448441; COSMIC: COSV59629428; COSMIC: COSV59629428;