rs17709314

Variant names:

• chr13-98826885-T-C
• rs17709314
• NM_001366683.2:c.4968A>G

Your query was ambiguous. Multiple possible variants found:

• chr13-98826885-T-C
• chr13-98826885-T-G

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.4968A>G​(p.Ala1656Ala) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,605,618 control chromosomes in the GnomAD database, including 9,619 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.077 (571 hom., cov: 33)
  • Exomes 𝑓: 0.11 (9048 hom.)
• Consequence: DOCK9 NM_001366683.2 splice_region, synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.687
• Publications: 14 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-AS1 (HGNC:40672): (DOCK9 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.038).
• BP7: Synonymous conserved (PhyloP=-0.687 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.112 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.4968A>G	p.Ala1656Ala	splice_region synonymous	Exon 44 of 53	NP_001353612.1	A0A804HIE8
	DOCK9	NM_001366681.2		c.4968A>G	p.Ala1656Ala	splice_region synonymous	Exon 44 of 55	NP_001353610.1
	DOCK9	NM_001366684.2		c.4968A>G	p.Ala1656Ala	splice_region synonymous	Exon 44 of 54	NP_001353613.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK9	ENST00000682017.1	MANE Select	c.4968A>G	p.Ala1656Ala	splice_region synonymous	Exon 44 of 53	ENSP00000507034.1	A0A804HIE8
	DOCK9	ENST00000903387.1		c.4968A>G	p.Ala1656Ala	splice_region synonymous	Exon 45 of 54	ENSP00000573446.1
	DOCK9	ENST00000448493.7	TSL:5	c.4935A>G	p.Ala1645Ala	splice_region synonymous	Exon 44 of 53	ENSP00000401958.4	A0A088AWN3

Frequencies

GnomAD3 genomes AF: 0.0767 AC: 11673 AN: 152202 Hom.: 570 Cov.: 33

Gnomad AFR AF: 0.0218

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.0683

Gnomad ASJ AF: 0.0790

Gnomad EAS AF: 0.000960

Gnomad SAS AF: 0.0553

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.0789

GnomAD2 exomes AF: 0.0799 AC: 19302 AN: 241662 AF XY: 0.0815

Gnomad AFR exome AF: 0.0209

Gnomad AMR exome AF: 0.0408

Gnomad ASJ exome AF: 0.0753

Gnomad EAS exome AF: 0.000398

Gnomad FIN exome AF: 0.113

Gnomad NFE exome AF: 0.112

Gnomad OTH exome AF: 0.0876

GnomAD4 exome AF: 0.106 AC: 153632 AN: 1453298 Hom.: 9048 Cov.: 29 AF XY: 0.105 AC XY: 75646 AN XY: 722552

African (AFR) AF: 0.0194 AC: 649 AN: 33436

American (AMR) AF: 0.0436 AC: 1924 AN: 44080

Ashkenazi Jewish (ASJ) AF: 0.0778 AC: 2027 AN: 26038

East Asian (EAS) AF: 0.000404 AC: 16 AN: 39626

South Asian (SAS) AF: 0.0589 AC: 4991 AN: 84776

European-Finnish (FIN) AF: 0.118 AC: 6291 AN: 53214

Middle Eastern (MID) AF: 0.0498 AC: 287 AN: 5758

European-Non Finnish (NFE) AF: 0.119 AC: 131673 AN: 1106236

Other (OTH) AF: 0.0960 AC: 5774 AN: 60134

GnomAD4 genome AF: 0.0766 AC: 11675 AN: 152320 Hom.: 571 Cov.: 33 AF XY: 0.0750 AC XY: 5584 AN XY: 74488

African (AFR) AF: 0.0217 AC: 904 AN: 41578

American (AMR) AF: 0.0682 AC: 1043 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0790 AC: 274 AN: 3470

East Asian (EAS) AF: 0.000963 AC: 5 AN: 5194

South Asian (SAS) AF: 0.0556 AC: 268 AN: 4822

European-Finnish (FIN) AF: 0.110 AC: 1164 AN: 10614

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7768 AN: 68018

Other (OTH) AF: 0.0781 AC: 165 AN: 2114

Alfa AF: 0.0969 Hom.: 1432

Bravo AF: 0.0706

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	4.2
DANN	Benign	0.71
PhyloP100		-0.69
Mutation Taster		=89/11	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: rs17709314; hg19: chr13-99479139;