chr13-98850006-G-A

Variant names:

• chr13-98850006-G-A
• rs2296990
• NM_001366683.2:c.4013+41C>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.4013+41C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0588 in 1,415,940 control chromosomes in the GnomAD database, including 3,695 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 0.051 (341 hom., cov: 32)
  • Exomes 𝑓: 0.060 (3354 hom.)
• Consequence: DOCK9 NM_001366683.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.601
• Publications: 4 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=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.174 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.4013+41C>T		intron	N/A	NP_001353612.1
	DOCK9	NM_001366681.2		c.4013+41C>T		intron	N/A	NP_001353610.1
	DOCK9	NM_001366684.2		c.4013+41C>T		intron	N/A	NP_001353613.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK9	ENST00000682017.1	MANE Select	c.4013+41C>T		intron	N/A	ENSP00000507034.1
	DOCK9	ENST00000448493.7	TSL:5	c.4049+41C>T		intron	N/A	ENSP00000401958.4
	DOCK9	ENST00000703211.1		c.4049+41C>T		intron	N/A	ENSP00000515238.1

Frequencies

GnomAD3 genomes AF: 0.0515 AC: 7822 AN: 151994 Hom.: 339 Cov.: 32

Gnomad AFR AF: 0.0156

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.0915

Gnomad ASJ AF: 0.0591

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.0413

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0496

Gnomad OTH AF: 0.0688

GnomAD2 exomes AF: 0.0820 AC: 13162 AN: 160464 AF XY: 0.0798

Gnomad AFR exome AF: 0.0152

Gnomad AMR exome AF: 0.167

Gnomad ASJ exome AF: 0.0639

Gnomad EAS exome AF: 0.179

Gnomad FIN exome AF: 0.0414

Gnomad NFE exome AF: 0.0504

Gnomad OTH exome AF: 0.0721

GnomAD4 exome AF: 0.0597 AC: 75417 AN: 1263826 Hom.: 3354 Cov.: 18 AF XY: 0.0607 AC XY: 38257 AN XY: 630180

African (AFR) AF: 0.0141 AC: 405 AN: 28818

American (AMR) AF: 0.154 AC: 5340 AN: 34586

Ashkenazi Jewish (ASJ) AF: 0.0665 AC: 1614 AN: 24280

East Asian (EAS) AF: 0.238 AC: 8507 AN: 35790

South Asian (SAS) AF: 0.103 AC: 7759 AN: 75454

European-Finnish (FIN) AF: 0.0406 AC: 2004 AN: 49410

Middle Eastern (MID) AF: 0.0974 AC: 525 AN: 5388

European-Non Finnish (NFE) AF: 0.0481 AC: 45964 AN: 956564

Other (OTH) AF: 0.0616 AC: 3299 AN: 53536

GnomAD4 genome AF: 0.0514 AC: 7826 AN: 152114 Hom.: 341 Cov.: 32 AF XY: 0.0540 AC XY: 4018 AN XY: 74362

African (AFR) AF: 0.0156 AC: 647 AN: 41496

American (AMR) AF: 0.0917 AC: 1403 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0591 AC: 205 AN: 3468

East Asian (EAS) AF: 0.184 AC: 950 AN: 5176

South Asian (SAS) AF: 0.116 AC: 560 AN: 4816

European-Finnish (FIN) AF: 0.0413 AC: 437 AN: 10574

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0496 AC: 3370 AN: 67970

Other (OTH) AF: 0.0691 AC: 146 AN: 2114

Alfa AF: 0.0526 Hom.: 192

Bravo AF: 0.0581

Asia WGS AF: 0.148 AC: 514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.6
DANN	Benign	0.70
PhyloP100		0.60
PromoterAI		-0.0049	Neutral
Mutation Taster		=21/79	disease causing

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: rs2296990; hg19: chr13-99502260; COSMIC: COSV59630276; COSMIC: COSV59630276;