NM_001366683.2:c.2382+23G>T

Variant names:

• chr13-98884948-C-A
• rs2274641
• NM_001366683.2:c.2382+23G>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.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
• Publications: 9 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.85 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK9	NM_001366683.2	MANE Select	c.2382+23G>T		intron	N/A	NP_001353612.1
	DOCK9	NM_001366681.2		c.2382+23G>T		intron	N/A	NP_001353610.1
	DOCK9	NM_001366684.2		c.2382+23G>T		intron	N/A	NP_001353613.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK9	ENST00000682017.1	MANE Select	c.2382+23G>T		intron	N/A	ENSP00000507034.1
	DOCK9	ENST00000427887.2	TSL:1	c.2385+23G>T		intron	N/A	ENSP00000413781.2
	DOCK9	ENST00000448493.7	TSL:5	c.2418+23G>T		intron	N/A	ENSP00000401958.4

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

GnomAD2 exomes AF: 0.750 AC: 177835 AN: 237088 AF XY: 0.760

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 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

African (AFR) AF: 0.564 AC: 18679 AN: 33112

American (AMR) AF: 0.766 AC: 32901 AN: 42978

Ashkenazi Jewish (ASJ) AF: 0.795 AC: 20525 AN: 25802

East Asian (EAS) AF: 0.583 AC: 23030 AN: 39510

South Asian (SAS) AF: 0.882 AC: 73917 AN: 83838

European-Finnish (FIN) AF: 0.727 AC: 38593 AN: 53088

Middle Eastern (MID) AF: 0.880 AC: 4971 AN: 5652

European-Non Finnish (NFE) AF: 0.778 AC: 859937 AN: 1106006

Other (OTH) AF: 0.765 AC: 45917 AN: 59994

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

African (AFR) AF: 0.575 AC: 23831 AN: 41466

American (AMR) AF: 0.754 AC: 11522 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.786 AC: 2726 AN: 3468

East Asian (EAS) AF: 0.524 AC: 2696 AN: 5148

South Asian (SAS) AF: 0.872 AC: 4199 AN: 4818

European-Finnish (FIN) AF: 0.719 AC: 7602 AN: 10570

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

European-Non Finnish (NFE) AF: 0.773 AC: 52572 AN: 67998

Other (OTH) AF: 0.760 AC: 1606 AN: 2112

Alfa AF: 0.729 Hom.: 8601

Bravo AF: 0.708

Asia WGS AF: 0.735 AC: 2551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.51
PhyloP100		0.066
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: rs2274641; hg19: chr13-99537202;