rs12429249

Positions:

• chr13-98925965-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001366683.2(DOCK9):​c.334-46G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,454,830 control chromosomes in the GnomAD database, including 22,546 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 0.15 (1971 hom., cov: 33)
  • Exomes 𝑓: 0.18 (20575 hom.)
• Consequence: DOCK9 NM_001366683.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK9	NM_001366683.2	c.334-46G>A		intron_variant		ENST00000682017.1	NP_001353612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK9	ENST00000682017.1	c.334-46G>A		intron_variant			NM_001366683.2	ENSP00000507034	P3

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23261 AN: 152048 Hom.: 1970 Cov.: 33

Gnomad AFR AF: 0.0863

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.177

GnomAD3 exomes AF: 0.188 AC: 23839 AN: 126960 Hom.: 2323 AF XY: 0.186 AC XY: 12606 AN XY: 67662

Gnomad AFR exome AF: 0.0844

Gnomad AMR exome AF: 0.231

Gnomad ASJ exome AF: 0.178

Gnomad EAS exome AF: 0.204

Gnomad SAS exome AF: 0.209

Gnomad FIN exome AF: 0.176

Gnomad NFE exome AF: 0.183

Gnomad OTH exome AF: 0.173

GnomAD4 exome AF: 0.176 AC: 228739 AN: 1302662 Hom.: 20575 Cov.: 19 AF XY: 0.176 AC XY: 113674 AN XY: 644156

Gnomad4 AFR exome AF: 0.0810

Gnomad4 AMR exome AF: 0.215

Gnomad4 ASJ exome AF: 0.175

Gnomad4 EAS exome AF: 0.245

Gnomad4 SAS exome AF: 0.208

Gnomad4 FIN exome AF: 0.170

Gnomad4 NFE exome AF: 0.173

Gnomad4 OTH exome AF: 0.173

GnomAD4 genome AF: 0.153 AC: 23270 AN: 152168 Hom.: 1971 Cov.: 33 AF XY: 0.153 AC XY: 11415 AN XY: 74386

Gnomad4 AFR AF: 0.0864

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.177

Alfa AF: 0.178 Hom.: 5080

Bravo AF: 0.152

Asia WGS AF: 0.208 AC: 723 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.15
DANN	Benign	0.32

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

Publications

LitVar

Other links and lift over

dbSNP: rs12429249; hg19: chr13-99578219; COSMIC: COSV59639086;