13-98925965-C-T

Variant names:

• chr13-98925965-C-T
• rs12429249
• NM_001366683.2:c.334-46G>A

Variant summary

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

The NM_001366683.2(DOCK9):​c.334-46G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,454,830 control chromosomes in the GnomAD database, including 22,546 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 0.15 (1971 hom., cov: 33)
  • Exomes 𝑓: 0.18 (20575 hom.)
• Consequence: DOCK9 NM_001366683.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK9	NM_001366683.2	c.334-46G>A		intron_variant	Intron 3 of 52	ENST00000682017.1	NP_001353612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK9	ENST00000682017.1	c.334-46G>A		intron_variant	Intron 3 of 52		NM_001366683.2	ENSP00000507034.1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23261 AN: 152048 Hom.: 1970 Cov.: 33

Gnomad AFR AF: 0.0863

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.177

GnomAD2 exomes AF: 0.188 AC: 23839 AN: 126960 AF XY: 0.186

Gnomad AFR exome AF: 0.0844

Gnomad AMR exome AF: 0.231

Gnomad ASJ exome AF: 0.178

Gnomad EAS exome AF: 0.204

Gnomad FIN exome AF: 0.176

Gnomad NFE exome AF: 0.183

Gnomad OTH exome AF: 0.173

GnomAD4 exome AF: 0.176 AC: 228739 AN: 1302662 Hom.: 20575 Cov.: 19 AF XY: 0.176 AC XY: 113674 AN XY: 644156

African (AFR) AF: 0.0810 AC: 2329 AN: 28744

American (AMR) AF: 0.215 AC: 6035 AN: 28104

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 4084 AN: 23292

East Asian (EAS) AF: 0.245 AC: 8686 AN: 35404

South Asian (SAS) AF: 0.208 AC: 14889 AN: 71712

European-Finnish (FIN) AF: 0.170 AC: 6554 AN: 38616

Middle Eastern (MID) AF: 0.202 AC: 1075 AN: 5334

European-Non Finnish (NFE) AF: 0.173 AC: 175607 AN: 1016720

Other (OTH) AF: 0.173 AC: 9480 AN: 54736

GnomAD4 genome AF: 0.153 AC: 23270 AN: 152168 Hom.: 1971 Cov.: 33 AF XY: 0.153 AC XY: 11415 AN XY: 74386

African (AFR) AF: 0.0864 AC: 3589 AN: 41522

American (AMR) AF: 0.164 AC: 2508 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 596 AN: 3472

East Asian (EAS) AF: 0.193 AC: 1000 AN: 5174

South Asian (SAS) AF: 0.213 AC: 1027 AN: 4826

European-Finnish (FIN) AF: 0.158 AC: 1670 AN: 10584

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12299 AN: 67978

Other (OTH) AF: 0.177 AC: 374 AN: 2116

Alfa AF: 0.173 Hom.: 7739

Bravo AF: 0.152

Asia WGS AF: 0.208 AC: 723 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.15
DANN	Benign	0.32
PhyloP100		-2.3
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: rs12429249; hg19: chr13-99578219; COSMIC: COSV59639086;