13-98810339-C-T

Variant names:

• chr13-98810339-C-T
• rs2282134
• NM_001366683.2:c.5131-48G>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.5131-48G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 1,600,096 control chromosomes in the GnomAD database, including 135,864 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 0.35 (10842 hom., cov: 31)
  • Exomes 𝑓: 0.41 (125022 hom.)
• Consequence: DOCK9 NM_001366683.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK9	NM_001366683.2	c.5131-48G>A		intron_variant	Intron 45 of 52	ENST00000682017.1	NP_001353612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK9	ENST00000682017.1	c.5131-48G>A		intron_variant	Intron 45 of 52		NM_001366683.2	ENSP00000507034.1

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53120 AN: 151864 Hom.: 10840 Cov.: 31

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.348

GnomAD2 exomes AF: 0.399 AC: 95571 AN: 239688 AF XY: 0.398

Gnomad AFR exome AF: 0.154

Gnomad AMR exome AF: 0.317

Gnomad ASJ exome AF: 0.388

Gnomad EAS exome AF: 0.677

Gnomad FIN exome AF: 0.494

Gnomad NFE exome AF: 0.427

Gnomad OTH exome AF: 0.388

GnomAD4 exome AF: 0.408 AC: 590675 AN: 1448114 Hom.: 125022 Cov.: 32 AF XY: 0.406 AC XY: 292418 AN XY: 719598

African (AFR) AF: 0.153 AC: 5078 AN: 33220

American (AMR) AF: 0.311 AC: 13780 AN: 44268

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 10009 AN: 25974

East Asian (EAS) AF: 0.678 AC: 26792 AN: 39518

South Asian (SAS) AF: 0.302 AC: 25870 AN: 85662

European-Finnish (FIN) AF: 0.488 AC: 23291 AN: 47700

Middle Eastern (MID) AF: 0.336 AC: 1794 AN: 5346

European-Non Finnish (NFE) AF: 0.416 AC: 460465 AN: 1106446

Other (OTH) AF: 0.393 AC: 23596 AN: 59980

GnomAD4 genome AF: 0.350 AC: 53148 AN: 151982 Hom.: 10842 Cov.: 31 AF XY: 0.352 AC XY: 26170 AN XY: 74294

African (AFR) AF: 0.165 AC: 6827 AN: 41460

American (AMR) AF: 0.301 AC: 4604 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1334 AN: 3470

East Asian (EAS) AF: 0.673 AC: 3466 AN: 5150

South Asian (SAS) AF: 0.320 AC: 1535 AN: 4800

European-Finnish (FIN) AF: 0.494 AC: 5212 AN: 10558

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.427 AC: 29040 AN: 67940

Other (OTH) AF: 0.348 AC: 735 AN: 2114

Alfa AF: 0.393 Hom.: 4520

Bravo AF: 0.328

Asia WGS AF: 0.430 AC: 1497 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.054
DANN	Benign	0.50
PhyloP100		-2.8
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: rs2282134; hg19: chr13-99462593; COSMIC: COSV59634053;