rs9554522

Variant names:

• chr13-98796187-T-A
• rs9554522
• NM_001366683.2:c.6156+928A>T

Your query was ambiguous. Multiple possible variants found:

• chr13-98796187-T-A
• chr13-98796187-T-G

Variant summary

Our verdict is Benign. The variant received -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
• 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 (EAS) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK9	NM_001366683.2	c.6156+928A>T		intron_variant	Intron 52 of 52	ENST00000682017.1	NP_001353612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK9	ENST00000682017.1	c.6156+928A>T		intron_variant	Intron 52 of 52		NM_001366683.2	ENSP00000507034.1

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

GnomAD2 exomes AF: 0.417 AC: 82593 AN: 197932 AF XY: 0.413

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 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

African (AFR) AF: 0.356 AC: 11424 AN: 32116

American (AMR) AF: 0.328 AC: 13173 AN: 40122

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 9845 AN: 25344

East Asian (EAS) AF: 0.599 AC: 22761 AN: 37978

South Asian (SAS) AF: 0.306 AC: 24653 AN: 80608

European-Finnish (FIN) AF: 0.488 AC: 24886 AN: 50984

Middle Eastern (MID) AF: 0.339 AC: 1919 AN: 5666

European-Non Finnish (NFE) AF: 0.439 AC: 471289 AN: 1073026

Other (OTH) AF: 0.419 AC: 24425 AN: 58360

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

African (AFR) AF: 0.368 AC: 15262 AN: 41462

American (AMR) AF: 0.331 AC: 5061 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1347 AN: 3472

East Asian (EAS) AF: 0.622 AC: 3212 AN: 5164

South Asian (SAS) AF: 0.323 AC: 1559 AN: 4828

European-Finnish (FIN) AF: 0.495 AC: 5228 AN: 10558

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.451 AC: 30667 AN: 67946

Other (OTH) AF: 0.400 AC: 845 AN: 2110

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
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9554522; hg19: chr13-99448441; COSMIC: COSV59629428; COSMIC: COSV59629428;