NM_001366683.2:c.2382+8C>A

Variant names:

• chr13-98884963-G-T
• rs2274642
• NM_001366683.2:c.2382+8C>A

Variant summary

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

The NM_001366683.2(DOCK9):​c.2382+8C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.762 in 1,609,406 control chromosomes in the GnomAD database, including 470,729 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 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 0.71 (39013 hom., cov: 32)
  • Exomes 𝑓: 0.77 (431716 hom.)
• Consequence: DOCK9 NM_001366683.2 splice_region, intron
• Scores: Splicing: ADA: 0.00005738
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790
• Publications: 10 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK9	NM_001366683.2	c.2382+8C>A		splice_region_variant, intron_variant	Intron 21 of 52	ENST00000682017.1	NP_001353612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK9	ENST00000682017.1	c.2382+8C>A		splice_region_variant, intron_variant	Intron 21 of 52		NM_001366683.2	ENSP00000507034.1

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107775 AN: 151914 Hom.: 38996 Cov.: 32

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.786

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.712

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.760

GnomAD2 exomes AF: 0.746 AC: 182181 AN: 244286 AF XY: 0.754

Gnomad AFR exome AF: 0.581

Gnomad AMR exome AF: 0.768

Gnomad ASJ exome AF: 0.789

Gnomad EAS exome AF: 0.512

Gnomad FIN exome AF: 0.718

Gnomad NFE exome AF: 0.773

Gnomad OTH exome AF: 0.770

GnomAD4 exome AF: 0.768 AC: 1118596 AN: 1457374 Hom.: 431716 Cov.: 40 AF XY: 0.770 AC XY: 557878 AN XY: 724672

African (AFR) AF: 0.579 AC: 19309 AN: 33348

American (AMR) AF: 0.767 AC: 33859 AN: 44172

Ashkenazi Jewish (ASJ) AF: 0.795 AC: 20700 AN: 26032

East Asian (EAS) AF: 0.583 AC: 23056 AN: 39566

South Asian (SAS) AF: 0.841 AC: 71900 AN: 85524

European-Finnish (FIN) AF: 0.722 AC: 38433 AN: 53260

Middle Eastern (MID) AF: 0.877 AC: 5011 AN: 5714

European-Non Finnish (NFE) AF: 0.776 AC: 860456 AN: 1109544

Other (OTH) AF: 0.762 AC: 45872 AN: 60214

GnomAD4 genome AF: 0.709 AC: 107830 AN: 152032 Hom.: 39013 Cov.: 32 AF XY: 0.708 AC XY: 52622 AN XY: 74334

African (AFR) AF: 0.587 AC: 24321 AN: 41426

American (AMR) AF: 0.755 AC: 11530 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.786 AC: 2728 AN: 3472

East Asian (EAS) AF: 0.522 AC: 2689 AN: 5152

South Asian (SAS) AF: 0.827 AC: 3982 AN: 4814

European-Finnish (FIN) AF: 0.712 AC: 7535 AN: 10582

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.771 AC: 52404 AN: 67992

Other (OTH) AF: 0.760 AC: 1605 AN: 2112

Alfa AF: 0.747 Hom.: 26990

Bravo AF: 0.710

Asia WGS AF: 0.699 AC: 2428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.49
DANN	Benign	0.27
PhyloP100		0.079
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000057
dbscSNV1_RF	Benign	0.0
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: rs2274642; hg19: chr13-99537217;