rs2296984

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr13-98805177-T-A
• chr13-98805177-T-C
• chr13-98805177-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001366683.2(DOCK9):​c.5547A>T​(p.Ala1849Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,450,886 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DOCK9 NM_001366683.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -8.87
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>T	p.Ala1849Ala	synonymous	Exon 49 of 53	NP_001353612.1
	DOCK9	NM_001366681.2		c.5652A>T	p.Ala1884Ala	synonymous	Exon 51 of 55	NP_001353610.1
	DOCK9	NM_001366684.2		c.5616A>T	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>T	p.Ala1849Ala	synonymous	Exon 49 of 53	ENSP00000507034.1
	DOCK9	ENST00000448493.7	TSL:5	c.5514A>T	p.Ala1838Ala	synonymous	Exon 49 of 53	ENSP00000401958.4
	DOCK9	ENST00000703211.1		c.5619A>T	p.Ala1873Ala	synonymous	Exon 51 of 56	ENSP00000515238.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1450886 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 720518

African (AFR) AF: 0.00 AC: 0 AN: 33386

American (AMR) AF: 0.0000230 AC: 1 AN: 43398

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25806

East Asian (EAS) AF: 0.00 AC: 0 AN: 39550

South Asian (SAS) AF: 0.00 AC: 0 AN: 84428

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52732

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105842

Other (OTH) AF: 0.00 AC: 0 AN: 59994

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.9
DANN	Benign	0.44
PhyloP100		-8.9

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.23		Position offset: -10

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2296984; hg19: chr13-99457431;