chr13-98942993-G-A

Variant names:

• chr13-98942993-G-A
• rs12872448
• NM_001366683.2:c.243+12442C>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.243+12442C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,196 control chromosomes in the GnomAD database, including 3,640 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 0.20 (3640 hom., cov: 33)
• Consequence: DOCK9 NM_001366683.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.324 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK9	NM_001366683.2	MANE Select	c.243+12442C>T		intron	N/A	NP_001353612.1	A0A804HIE8
	DOCK9	NM_001366681.2		c.243+12442C>T		intron	N/A	NP_001353610.1
	DOCK9	NM_001366684.2		c.243+12442C>T		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.243+12442C>T		intron	N/A	ENSP00000507034.1	A0A804HIE8
	DOCK9	ENST00000427887.2	TSL:1	c.246+12442C>T		intron	N/A	ENSP00000413781.2	A0A0A0MT38
	DOCK9	ENST00000903387.1		c.243+12442C>T		intron	N/A	ENSP00000573446.1

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30618 AN: 152078 Hom.: 3625 Cov.: 33

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.224

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.202 AC: 30681 AN: 152196 Hom.: 3640 Cov.: 33 AF XY: 0.202 AC XY: 15037 AN XY: 74430

African (AFR) AF: 0.329 AC: 13643 AN: 41486

American (AMR) AF: 0.211 AC: 3227 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 665 AN: 3470

East Asian (EAS) AF: 0.120 AC: 623 AN: 5182

South Asian (SAS) AF: 0.257 AC: 1241 AN: 4826

European-Finnish (FIN) AF: 0.104 AC: 1104 AN: 10602

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9469 AN: 68012

Other (OTH) AF: 0.228 AC: 481 AN: 2112

Alfa AF: 0.159 Hom.: 9426

Bravo AF: 0.215

Asia WGS AF: 0.217 AC: 752 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.13
DANN	Benign	0.61
PhyloP100		-1.2
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: rs12872448; hg19: chr13-99595247;