13-98829776-G-C

Variant names:

• chr13-98829776-G-C
• rs9517459
• NM_001366683.2:c.4636-20C>G

Variant summary

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

The NM_001366683.2(DOCK9):​c.4636-20C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 1,573,730 control chromosomes in the GnomAD database, including 40,015 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.21 (3576 hom., cov: 32)
  • Exomes 𝑓: 0.22 (36439 hom.)
• Consequence: DOCK9 NM_001366683.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.532
• Publications: 8 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 -12 ACMG points.

• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 2 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK9	NM_001366683.2	c.4636-20C>G		intron_variant	Intron 41 of 52	ENST00000682017.1	NP_001353612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK9	ENST00000682017.1	c.4636-20C>G		intron_variant	Intron 41 of 52		NM_001366683.2	ENSP00000507034.1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31422 AN: 152004 Hom.: 3569 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.186

GnomAD2 exomes AF: 0.211 AC: 41977 AN: 199348 AF XY: 0.209

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.107

Gnomad ASJ exome AF: 0.206

Gnomad EAS exome AF: 0.443

Gnomad FIN exome AF: 0.243

Gnomad NFE exome AF: 0.235

Gnomad OTH exome AF: 0.211

GnomAD4 exome AF: 0.220 AC: 313354 AN: 1421606 Hom.: 36439 Cov.: 28 AF XY: 0.218 AC XY: 153662 AN XY: 704310

African (AFR) AF: 0.161 AC: 5253 AN: 32722

American (AMR) AF: 0.107 AC: 4297 AN: 40272

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 5090 AN: 25504

East Asian (EAS) AF: 0.349 AC: 13393 AN: 38428

South Asian (SAS) AF: 0.107 AC: 8677 AN: 81376

European-Finnish (FIN) AF: 0.241 AC: 12381 AN: 51404

Middle Eastern (MID) AF: 0.124 AC: 708 AN: 5714

European-Non Finnish (NFE) AF: 0.231 AC: 250945 AN: 1087158

Other (OTH) AF: 0.214 AC: 12610 AN: 59028

GnomAD4 genome AF: 0.207 AC: 31470 AN: 152124 Hom.: 3576 Cov.: 32 AF XY: 0.206 AC XY: 15296 AN XY: 74372

African (AFR) AF: 0.164 AC: 6794 AN: 41524

American (AMR) AF: 0.147 AC: 2247 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 682 AN: 3470

East Asian (EAS) AF: 0.423 AC: 2181 AN: 5160

South Asian (SAS) AF: 0.114 AC: 550 AN: 4816

European-Finnish (FIN) AF: 0.240 AC: 2538 AN: 10572

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.233 AC: 15825 AN: 67974

Other (OTH) AF: 0.186 AC: 393 AN: 2108

Alfa AF: 0.218 Hom.: 718

Bravo AF: 0.197

Asia WGS AF: 0.220 AC: 769 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.9
DANN	Benign	0.58
PhyloP100		0.53
BranchPoint Hunter		2.0
PromoterAI		-0.0086	Neutral
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: rs9517459; hg19: chr13-99482030; COSMIC: COSV59622264; COSMIC: COSV59622264;