rs2296994

Variant names:

• chr13-98881643-G-A
• rs2296994
• NM_001366683.2:c.2676-16C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-98881643-G-A
• chr13-98881643-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001366683.2(DOCK9):​c.2676-16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,598,088 control chromosomes in the GnomAD database, including 14,532 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 0.12 (1215 hom., cov: 32)
  • Exomes 𝑓: 0.13 (13317 hom.)
• Consequence: DOCK9 NM_001366683.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.346
• Publications: 12 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=-0.54).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.19 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.2676-16C>T		intron	N/A	NP_001353612.1	A0A804HIE8
	DOCK9	NM_001366681.2		c.2676-16C>T		intron	N/A	NP_001353610.1
	DOCK9	NM_001366684.2		c.2676-16C>T		intron	N/A	NP_001353613.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK9	ENST00000682017.1	MANE Select	c.2676-16C>T		intron	N/A	ENSP00000507034.1	A0A804HIE8
	DOCK9	ENST00000427887.2	TSL:1	c.2679-16C>T		intron	N/A	ENSP00000413781.2	A0A0A0MT38
	DOCK9	ENST00000903387.1		c.2769-16C>T		intron	N/A	ENSP00000573446.1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18368 AN: 152082 Hom.: 1213 Cov.: 32

Gnomad AFR AF: 0.0744

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.143

GnomAD2 exomes AF: 0.153 AC: 34516 AN: 225958 AF XY: 0.152

Gnomad AFR exome AF: 0.0751

Gnomad AMR exome AF: 0.215

Gnomad ASJ exome AF: 0.151

Gnomad EAS exome AF: 0.200

Gnomad FIN exome AF: 0.120

Gnomad NFE exome AF: 0.132

Gnomad OTH exome AF: 0.144

GnomAD4 exome AF: 0.130 AC: 188313 AN: 1445888 Hom.: 13317 Cov.: 30 AF XY: 0.132 AC XY: 94983 AN XY: 717460

African (AFR) AF: 0.0717 AC: 2386 AN: 33270

American (AMR) AF: 0.203 AC: 8644 AN: 42682

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 3873 AN: 25792

East Asian (EAS) AF: 0.242 AC: 9521 AN: 39292

South Asian (SAS) AF: 0.192 AC: 15894 AN: 82902

European-Finnish (FIN) AF: 0.123 AC: 6476 AN: 52728

Middle Eastern (MID) AF: 0.190 AC: 1090 AN: 5748

European-Non Finnish (NFE) AF: 0.120 AC: 132438 AN: 1103562

Other (OTH) AF: 0.133 AC: 7991 AN: 59912

GnomAD4 genome AF: 0.121 AC: 18373 AN: 152200 Hom.: 1215 Cov.: 32 AF XY: 0.122 AC XY: 9094 AN XY: 74422

African (AFR) AF: 0.0744 AC: 3089 AN: 41536

American (AMR) AF: 0.141 AC: 2163 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 515 AN: 3470

East Asian (EAS) AF: 0.192 AC: 993 AN: 5182

South Asian (SAS) AF: 0.200 AC: 964 AN: 4816

European-Finnish (FIN) AF: 0.114 AC: 1203 AN: 10586

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8951 AN: 68008

Other (OTH) AF: 0.143 AC: 301 AN: 2108

Alfa AF: 0.133 Hom.: 537

Bravo AF: 0.122

Asia WGS AF: 0.204 AC: 706 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Benign	0.55
PhyloP100		0.35
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: rs2296994; hg19: chr13-99533897; COSMIC: COSV59630285;