rs9517474

Variant names:

• chr13-98883777-G-A
• rs9517474
• NM_001366683.2:c.2469+36C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-98883777-G-A
• chr13-98883777-G-C
• chr13-98883777-G-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.2469+36C>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 1,437,178 control chromosomes in the GnomAD database, including 424,555 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 (39088 hom., cov: 33)
  • Exomes 𝑓: 0.77 (385467 hom.)
• Consequence: DOCK9 NM_001366683.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.233
• Publications: 13 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=-0.95).
• 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 rank	MANE	Protein	UniProt
DOCK9	NM_001366683.2	c.2469+36C>T		intron_variant	Intron 22 of 52	ENST00000682017.1	NP_001353612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK9	ENST00000682017.1	c.2469+36C>T		intron_variant	Intron 22 of 52		NM_001366683.2	ENSP00000507034.1

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107751 AN: 151982 Hom.: 39070 Cov.: 33

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.786

Gnomad EAS AF: 0.523

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

GnomAD2 exomes AF: 0.751 AC: 143063 AN: 190576 AF XY: 0.760

Gnomad AFR exome AF: 0.574

Gnomad AMR exome AF: 0.771

Gnomad ASJ exome AF: 0.792

Gnomad EAS exome AF: 0.525

Gnomad FIN exome AF: 0.726

Gnomad NFE exome AF: 0.777

Gnomad OTH exome AF: 0.772

GnomAD4 exome AF: 0.772 AC: 992108 AN: 1285078 Hom.: 385467 Cov.: 16 AF XY: 0.775 AC XY: 496744 AN XY: 641054

African (AFR) AF: 0.566 AC: 16284 AN: 28764

American (AMR) AF: 0.767 AC: 23961 AN: 31250

Ashkenazi Jewish (ASJ) AF: 0.797 AC: 18288 AN: 22936

East Asian (EAS) AF: 0.588 AC: 22202 AN: 37784

South Asian (SAS) AF: 0.882 AC: 63885 AN: 72446

European-Finnish (FIN) AF: 0.728 AC: 37535 AN: 51562

Middle Eastern (MID) AF: 0.880 AC: 4691 AN: 5332

European-Non Finnish (NFE) AF: 0.779 AC: 763840 AN: 980960

Other (OTH) AF: 0.766 AC: 41422 AN: 54044

GnomAD4 genome AF: 0.709 AC: 107808 AN: 152100 Hom.: 39088 Cov.: 33 AF XY: 0.709 AC XY: 52688 AN XY: 74358

African (AFR) AF: 0.575 AC: 23823 AN: 41458

American (AMR) AF: 0.754 AC: 11525 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.786 AC: 2728 AN: 3470

East Asian (EAS) AF: 0.523 AC: 2700 AN: 5164

South Asian (SAS) AF: 0.872 AC: 4204 AN: 4822

European-Finnish (FIN) AF: 0.719 AC: 7613 AN: 10586

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.773 AC: 52574 AN: 67990

Other (OTH) AF: 0.761 AC: 1607 AN: 2112

Alfa AF: 0.757 Hom.: 188276

Bravo AF: 0.708

Asia WGS AF: 0.734 AC: 2548 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.0
DANN	Benign	0.38
PhyloP100		-0.23
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: rs9517474; hg19: chr13-99536031;