rs9557078

Variant names:

• chr13-98807637-A-C
• rs9557078
• NM_001366683.2:c.5514+24T>G

Your query was ambiguous. Multiple possible variants found:

• chr13-98807637-A-C
• chr13-98807637-A-G
• chr13-98807637-A-T

Variant summary

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

The NM_001366683.2(DOCK9):​c.5514+24T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 1,568,862 control chromosomes in the GnomAD database, including 140,170 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 0.41 (13458 hom., cov: 32)
  • Exomes 𝑓: 0.42 (126712 hom.)
• Consequence: DOCK9 NM_001366683.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0520
• Publications: 10 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=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK9	NM_001366683.2	c.5514+24T>G		intron_variant	Intron 48 of 52	ENST00000682017.1	NP_001353612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK9	ENST00000682017.1	c.5514+24T>G		intron_variant	Intron 48 of 52		NM_001366683.2	ENSP00000507034.1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62758 AN: 151920 Hom.: 13446 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.400

GnomAD2 exomes AF: 0.420 AC: 102624 AN: 244190 AF XY: 0.416

Gnomad AFR exome AF: 0.373

Gnomad AMR exome AF: 0.330

Gnomad ASJ exome AF: 0.390

Gnomad EAS exome AF: 0.679

Gnomad FIN exome AF: 0.491

Gnomad NFE exome AF: 0.430

Gnomad OTH exome AF: 0.400

GnomAD4 exome AF: 0.417 AC: 591175 AN: 1416824 Hom.: 126712 Cov.: 30 AF XY: 0.415 AC XY: 290534 AN XY: 699722

African (AFR) AF: 0.371 AC: 12141 AN: 32720

American (AMR) AF: 0.325 AC: 14043 AN: 43168

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 9789 AN: 25400

East Asian (EAS) AF: 0.678 AC: 26491 AN: 39048

South Asian (SAS) AF: 0.316 AC: 25099 AN: 79346

European-Finnish (FIN) AF: 0.488 AC: 25407 AN: 52106

Middle Eastern (MID) AF: 0.346 AC: 1950 AN: 5634

European-Non Finnish (NFE) AF: 0.418 AC: 452276 AN: 1080990

Other (OTH) AF: 0.411 AC: 23979 AN: 58412

GnomAD4 genome AF: 0.413 AC: 62813 AN: 152038 Hom.: 13458 Cov.: 32 AF XY: 0.414 AC XY: 30793 AN XY: 74304

African (AFR) AF: 0.376 AC: 15600 AN: 41456

American (AMR) AF: 0.326 AC: 4990 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1338 AN: 3468

East Asian (EAS) AF: 0.674 AC: 3492 AN: 5180

South Asian (SAS) AF: 0.337 AC: 1622 AN: 4814

European-Finnish (FIN) AF: 0.494 AC: 5212 AN: 10540

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.431 AC: 29315 AN: 67978

Other (OTH) AF: 0.400 AC: 844 AN: 2112

Alfa AF: 0.418 Hom.: 32384

Bravo AF: 0.398

Asia WGS AF: 0.452 AC: 1574 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.3
DANN	Benign	0.80
PhyloP100		0.052
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: rs9557078; hg19: chr13-99459891; COSMIC: COSV59638800; COSMIC: COSV59638800;