13-98884948-C-A

Position:

• chr13-98884948-C-A

Variant summary

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

The NM_001366683.2(DOCK9):​c.2382+23G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 1,602,048 control chromosomes in the GnomAD database, including 473,277 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 0.71 (39077 hom., cov: 32)
  • Exomes 𝑓: 0.77 (434200 hom.)
• Consequence: DOCK9 NM_001366683.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK9	NM_001366683.2	c.2382+23G>T		intron_variant		ENST00000682017.1	NP_001353612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK9	ENST00000682017.1	c.2382+23G>T		intron_variant			NM_001366683.2	ENSP00000507034	P3

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107733 AN: 151950 Hom.: 39059 Cov.: 32

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.786

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.872

Gnomad FIN AF: 0.719

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.758

GnomAD3 exomes AF: 0.750 AC: 177835 AN: 237088 Hom.: 67840 AF XY: 0.760 AC XY: 97518 AN XY: 128284

Gnomad AFR exome AF: 0.565

Gnomad AMR exome AF: 0.768

Gnomad ASJ exome AF: 0.789

Gnomad EAS exome AF: 0.511

Gnomad SAS exome AF: 0.885

Gnomad FIN exome AF: 0.723

Gnomad NFE exome AF: 0.774

Gnomad OTH exome AF: 0.773

GnomAD4 exome AF: 0.771 AC: 1118470 AN: 1449980 Hom.: 434200 Cov.: 34 AF XY: 0.775 AC XY: 558073 AN XY: 720382

Gnomad4 AFR exome AF: 0.564

Gnomad4 AMR exome AF: 0.766

Gnomad4 ASJ exome AF: 0.795

Gnomad4 EAS exome AF: 0.583

Gnomad4 SAS exome AF: 0.882

Gnomad4 FIN exome AF: 0.727

Gnomad4 NFE exome AF: 0.778

Gnomad4 OTH exome AF: 0.765

GnomAD4 genome AF: 0.709 AC: 107790 AN: 152068 Hom.: 39077 Cov.: 32 AF XY: 0.709 AC XY: 52675 AN XY: 74328

Gnomad4 AFR AF: 0.575

Gnomad4 AMR AF: 0.754

Gnomad4 ASJ AF: 0.786

Gnomad4 EAS AF: 0.524

Gnomad4 SAS AF: 0.872

Gnomad4 FIN AF: 0.719

Gnomad4 NFE AF: 0.773

Gnomad4 OTH AF: 0.760

Alfa AF: 0.733 Hom.: 8460

Bravo AF: 0.708

Asia WGS AF: 0.735 AC: 2551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.51

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: rs2274641; hg19: chr13-99537202;