chr13-98888141-A-G

Variant names:

• chr13-98888141-A-G
• rs1928104
• NM_001366683.2:c.2043+17T>C

Variant summary

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

The NM_001366681.2(DOCK9):​c.2043+17T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.764 in 1,556,262 control chromosomes in the GnomAD database, including 457,611 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 (38897 hom., cov: 32)
  • Exomes 𝑓: 0.77 (418714 hom.)
• Consequence: DOCK9 NM_001366681.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147
• 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=-0.85).
• 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_001366681.2. 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.2043+17T>C		intron	N/A	NP_001353612.1
	DOCK9	NM_001366681.2		c.2043+17T>C		intron	N/A	NP_001353610.1
	DOCK9	NM_001366684.2		c.2043+17T>C		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.2043+17T>C		intron	N/A	ENSP00000507034.1
	DOCK9	ENST00000427887.2	TSL:1	c.2046+17T>C		intron	N/A	ENSP00000413781.2
	DOCK9	ENST00000903387.1		c.2043+17T>C		intron	N/A	ENSP00000573446.1

Frequencies

GnomAD3 genomes AF: 0.707 AC: 107476 AN: 151952 Hom.: 38877 Cov.: 32

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.753

Gnomad ASJ AF: 0.784

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.872

Gnomad FIN AF: 0.712

Gnomad MID AF: 0.895

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.757

GnomAD2 exomes AF: 0.752 AC: 147971 AN: 196662 AF XY: 0.761

Gnomad AFR exome AF: 0.573

Gnomad AMR exome AF: 0.775

Gnomad ASJ exome AF: 0.793

Gnomad EAS exome AF: 0.526

Gnomad FIN exome AF: 0.720

Gnomad NFE exome AF: 0.775

Gnomad OTH exome AF: 0.775

GnomAD4 exome AF: 0.770 AC: 1080904 AN: 1404190 Hom.: 418714 Cov.: 25 AF XY: 0.773 AC XY: 538485 AN XY: 696874

African (AFR) AF: 0.566 AC: 17615 AN: 31114

American (AMR) AF: 0.772 AC: 27732 AN: 35920

Ashkenazi Jewish (ASJ) AF: 0.796 AC: 19780 AN: 24860

East Asian (EAS) AF: 0.584 AC: 22743 AN: 38912

South Asian (SAS) AF: 0.882 AC: 68934 AN: 78116

European-Finnish (FIN) AF: 0.722 AC: 36980 AN: 51216

Middle Eastern (MID) AF: 0.879 AC: 4789 AN: 5446

European-Non Finnish (NFE) AF: 0.775 AC: 837786 AN: 1080354

Other (OTH) AF: 0.765 AC: 44545 AN: 58252

GnomAD4 genome AF: 0.707 AC: 107536 AN: 152072 Hom.: 38897 Cov.: 32 AF XY: 0.707 AC XY: 52527 AN XY: 74322

African (AFR) AF: 0.575 AC: 23859 AN: 41470

American (AMR) AF: 0.753 AC: 11508 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.784 AC: 2719 AN: 3468

East Asian (EAS) AF: 0.523 AC: 2712 AN: 5182

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

European-Finnish (FIN) AF: 0.712 AC: 7514 AN: 10554

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

European-Non Finnish (NFE) AF: 0.771 AC: 52387 AN: 67986

Other (OTH) AF: 0.759 AC: 1602 AN: 2110

Alfa AF: 0.740 Hom.: 8023

Bravo AF: 0.707

Asia WGS AF: 0.734 AC: 2549 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	0.92
DANN	Benign	0.30
PhyloP100		-0.15
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: rs1928104; hg19: chr13-99540395; COSMIC: COSV59622979;