rs62620184

Variant names:

• chr13-98902367-G-A
• rs62620184
• NM_001366683.2:c.1301C>T
• DOCK9 p.Ala434Val

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001366683.2(DOCK9):​c.1301C>T​(p.Ala434Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0437 in 1,613,954 control chromosomes in the GnomAD database, including 1,873 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (136 hom., cov: 33)
  • Exomes 𝑓: 0.045 (1737 hom.)
• Consequence: DOCK9 NM_001366683.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.62
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0022068322).
• BP6: Variant 13-98902367-G-A is Benign according to our data. Variant chr13-98902367-G-A is described in ClinVar as Benign. ClinVar VariationId is 402794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0769 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.1301C>T	p.Ala434Val	missense	Exon 12 of 53	NP_001353612.1	A0A804HIE8
	DOCK9	NM_001366681.2		c.1301C>T	p.Ala434Val	missense	Exon 12 of 55	NP_001353610.1
	DOCK9	NM_001366684.2		c.1301C>T	p.Ala434Val	missense	Exon 12 of 54	NP_001353613.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK9	ENST00000682017.1	MANE Select	c.1301C>T	p.Ala434Val	missense	Exon 12 of 53	ENSP00000507034.1	A0A804HIE8
	DOCK9	ENST00000427887.2	TSL:1	c.1304C>T	p.Ala435Val	missense	Exon 12 of 33	ENSP00000413781.2	A0A0A0MT38
	DOCK9	ENST00000903387.1		c.1301C>T	p.Ala434Val	missense	Exon 12 of 54	ENSP00000573446.1

Frequencies

GnomAD3 genomes AF: 0.0336 AC: 5109 AN: 152186 Hom.: 135 Cov.: 33

Gnomad AFR AF: 0.00866

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0361

Gnomad ASJ AF: 0.0533

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0830

Gnomad FIN AF: 0.0400

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0446

Gnomad OTH AF: 0.0344

GnomAD2 exomes AF: 0.0432 AC: 10763 AN: 249154 AF XY: 0.0468

Gnomad AFR exome AF: 0.00684

Gnomad AMR exome AF: 0.0262

Gnomad ASJ exome AF: 0.0512

Gnomad EAS exome AF: 0.000835

Gnomad FIN exome AF: 0.0395

Gnomad NFE exome AF: 0.0473

Gnomad OTH exome AF: 0.0481

GnomAD4 exome AF: 0.0448 AC: 65431 AN: 1461650 Hom.: 1737 Cov.: 32 AF XY: 0.0463 AC XY: 33647 AN XY: 727116

African (AFR) AF: 0.00857 AC: 287 AN: 33480

American (AMR) AF: 0.0264 AC: 1182 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0534 AC: 1396 AN: 26136

East Asian (EAS) AF: 0.000453 AC: 18 AN: 39696

South Asian (SAS) AF: 0.0868 AC: 7487 AN: 86256

European-Finnish (FIN) AF: 0.0391 AC: 2087 AN: 53386

Middle Eastern (MID) AF: 0.0860 AC: 496 AN: 5768

European-Non Finnish (NFE) AF: 0.0447 AC: 49719 AN: 1111836

Other (OTH) AF: 0.0457 AC: 2759 AN: 60370

GnomAD4 genome AF: 0.0336 AC: 5110 AN: 152304 Hom.: 136 Cov.: 33 AF XY: 0.0340 AC XY: 2535 AN XY: 74462

African (AFR) AF: 0.00866 AC: 360 AN: 41564

American (AMR) AF: 0.0360 AC: 551 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0533 AC: 185 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5184

South Asian (SAS) AF: 0.0836 AC: 403 AN: 4818

European-Finnish (FIN) AF: 0.0400 AC: 425 AN: 10616

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0446 AC: 3035 AN: 68032

Other (OTH) AF: 0.0327 AC: 69 AN: 2112

Alfa AF: 0.0407 Hom.: 484

Bravo AF: 0.0308

Asia WGS AF: 0.0370 AC: 129 AN: 3478

EpiCase AF: 0.0465

EpiControl AF: 0.0479

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.85	D
MetaRNN	Benign	0.0022	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.6
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.035
Sift	Benign	0.14	T
Sift4G	Benign	0.25	T
gMVP		0.12
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs62620184;

hg19: chr13-99554621;