13-98805177-T-G

Variant names:

• chr13-98805177-T-G
• rs2296984
• NM_001366683.2:c.5547A>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001366683.2(DOCK9):​c.5547A>C​(p.Ala1849Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,602,684 control chromosomes in the GnomAD database, including 32,263 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 (3169 hom., cov: 32)
  • Exomes 𝑓: 0.20 (29094 hom.)
• Consequence: DOCK9 NM_001366683.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -8.87
• Publications: 22 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.028).
• BP7: Synonymous conserved (PhyloP=-8.87 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.211 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.5547A>C	p.Ala1849Ala	synonymous	Exon 49 of 53	NP_001353612.1
	DOCK9	NM_001366681.2		c.5652A>C	p.Ala1884Ala	synonymous	Exon 51 of 55	NP_001353610.1
	DOCK9	NM_001366684.2		c.5616A>C	p.Ala1872Ala	synonymous	Exon 50 of 54	NP_001353613.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK9	ENST00000682017.1	MANE Select	c.5547A>C	p.Ala1849Ala	synonymous	Exon 49 of 53	ENSP00000507034.1
	DOCK9	ENST00000448493.7	TSL:5	c.5514A>C	p.Ala1838Ala	synonymous	Exon 49 of 53	ENSP00000401958.4
	DOCK9	ENST00000703211.1		c.5619A>C	p.Ala1873Ala	synonymous	Exon 51 of 56	ENSP00000515238.1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30933 AN: 152090 Hom.: 3164 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.214

GnomAD2 exomes AF: 0.206 AC: 47876 AN: 232188 AF XY: 0.204

Gnomad AFR exome AF: 0.217

Gnomad AMR exome AF: 0.226

Gnomad ASJ exome AF: 0.190

Gnomad EAS exome AF: 0.191

Gnomad FIN exome AF: 0.198

Gnomad NFE exome AF: 0.204

Gnomad OTH exome AF: 0.196

GnomAD4 exome AF: 0.200 AC: 289877 AN: 1450474 Hom.: 29094 Cov.: 34 AF XY: 0.200 AC XY: 144304 AN XY: 720308

African (AFR) AF: 0.215 AC: 7188 AN: 33382

American (AMR) AF: 0.218 AC: 9431 AN: 43358

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 4829 AN: 25806

East Asian (EAS) AF: 0.238 AC: 9397 AN: 39542

South Asian (SAS) AF: 0.210 AC: 17736 AN: 84404

European-Finnish (FIN) AF: 0.201 AC: 10567 AN: 52700

Middle Eastern (MID) AF: 0.233 AC: 1338 AN: 5750

European-Non Finnish (NFE) AF: 0.197 AC: 217603 AN: 1105550

Other (OTH) AF: 0.197 AC: 11788 AN: 59982

GnomAD4 genome AF: 0.203 AC: 30952 AN: 152210 Hom.: 3169 Cov.: 32 AF XY: 0.203 AC XY: 15099 AN XY: 74418

African (AFR) AF: 0.214 AC: 8897 AN: 41520

American (AMR) AF: 0.173 AC: 2646 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 616 AN: 3472

East Asian (EAS) AF: 0.191 AC: 991 AN: 5182

South Asian (SAS) AF: 0.217 AC: 1046 AN: 4824

European-Finnish (FIN) AF: 0.198 AC: 2103 AN: 10596

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13953 AN: 68012

Other (OTH) AF: 0.213 AC: 450 AN: 2110

Alfa AF: 0.204 Hom.: 10366

Bravo AF: 0.202

Asia WGS AF: 0.214 AC: 741 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.28
DANN	Benign	0.40
PhyloP100		-8.9
Mutation Taster		=87/13	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2296984; hg19: chr13-99457431; COSMIC: COSV59620244; COSMIC: COSV59620244;