13-98853378-C-T

Variant names:

• chr13-98853378-C-T
• rs9513497
• NM_001366683.2:c.3946+30G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001366683.2(DOCK9):​c.3946+30G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 1,464,336 control chromosomes in the GnomAD database, including 190,053 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 0.47 (17452 hom., cov: 32)
  • Exomes 𝑓: 0.51 (172601 hom.)
• Consequence: DOCK9 NM_001366683.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100
• Publications: 8 publications found

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]

DOCK9 Gene-Disease associations (from GenCC):

• keratoconus

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366683.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK9	NM_001366683.2	MANE Select	c.3946+30G>A		intron	N/A	NP_001353612.1	A0A804HIE8
	DOCK9	NM_001366681.2		c.3946+30G>A		intron	N/A	NP_001353610.1
	DOCK9	NM_001366684.2		c.3946+30G>A		intron	N/A	NP_001353613.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK9	ENST00000682017.1	MANE Select	c.3946+30G>A		intron	N/A	ENSP00000507034.1	A0A804HIE8
	DOCK9	ENST00000903387.1		c.4039+30G>A		intron	N/A	ENSP00000573446.1
	DOCK9	ENST00000448493.7	TSL:5	c.3982+30G>A		intron	N/A	ENSP00000401958.4	A0A088AWN3

Frequencies

GnomAD3 genomes AF: 0.474 AC: 72014 AN: 151830 Hom.: 17454 Cov.: 32

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.496

GnomAD2 exomes AF: 0.475 AC: 106631 AN: 224638 AF XY: 0.476

Gnomad AFR exome AF: 0.401

Gnomad AMR exome AF: 0.496

Gnomad ASJ exome AF: 0.471

Gnomad EAS exome AF: 0.269

Gnomad FIN exome AF: 0.506

Gnomad NFE exome AF: 0.514

Gnomad OTH exome AF: 0.506

GnomAD4 exome AF: 0.508 AC: 666325 AN: 1312388 Hom.: 172601 Cov.: 17 AF XY: 0.505 AC XY: 332352 AN XY: 658124

African (AFR) AF: 0.398 AC: 11753 AN: 29510

American (AMR) AF: 0.501 AC: 18887 AN: 37694

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 11367 AN: 24240

East Asian (EAS) AF: 0.251 AC: 9604 AN: 38194

South Asian (SAS) AF: 0.434 AC: 33708 AN: 77694

European-Finnish (FIN) AF: 0.509 AC: 26948 AN: 52934

Middle Eastern (MID) AF: 0.522 AC: 2860 AN: 5480

European-Non Finnish (NFE) AF: 0.528 AC: 523853 AN: 991542

Other (OTH) AF: 0.496 AC: 27345 AN: 55100

GnomAD4 genome AF: 0.474 AC: 72031 AN: 151948 Hom.: 17452 Cov.: 32 AF XY: 0.472 AC XY: 35066 AN XY: 74262

African (AFR) AF: 0.404 AC: 16733 AN: 41418

American (AMR) AF: 0.526 AC: 8029 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1635 AN: 3472

East Asian (EAS) AF: 0.271 AC: 1399 AN: 5156

South Asian (SAS) AF: 0.418 AC: 2010 AN: 4812

European-Finnish (FIN) AF: 0.510 AC: 5381 AN: 10550

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.517 AC: 35142 AN: 67950

Other (OTH) AF: 0.497 AC: 1049 AN: 2110

Alfa AF: 0.497 Hom.: 10194

Bravo AF: 0.477

Asia WGS AF: 0.357 AC: 1240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.8
DANN	Benign	0.60
PhyloP100		-0.010
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9513497; hg19: chr13-99505632;