rs7995432

Positions:

• chr13-98920911-T-C

Variant summary

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

The NM_001366683.2(DOCK9):​c.717+43A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0435 in 1,546,418 control chromosomes in the GnomAD database, including 2,140 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 0.069 (594 hom., cov: 33)
  • Exomes 𝑓: 0.041 (1546 hom.)
• Consequence: DOCK9 NM_001366683.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0360

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK9	NM_001366683.2	c.717+43A>G		intron_variant		ENST00000682017.1	NP_001353612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK9	ENST00000682017.1	c.717+43A>G		intron_variant			NM_001366683.2	ENSP00000507034	P3

Frequencies

GnomAD3 genomes AF: 0.0689 AC: 10489 AN: 152190 Hom.: 594 Cov.: 33

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0424

Gnomad ASJ AF: 0.0259

Gnomad EAS AF: 0.0469

Gnomad SAS AF: 0.0634

Gnomad FIN AF: 0.0172

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0347

Gnomad OTH AF: 0.0621

GnomAD3 exomes AF: 0.0432 AC: 8085 AN: 187266 Hom.: 294 AF XY: 0.0434 AC XY: 4363 AN XY: 100594

Gnomad AFR exome AF: 0.156

Gnomad AMR exome AF: 0.0238

Gnomad ASJ exome AF: 0.0251

Gnomad EAS exome AF: 0.0346

Gnomad SAS exome AF: 0.0683

Gnomad FIN exome AF: 0.0178

Gnomad NFE exome AF: 0.0341

Gnomad OTH exome AF: 0.0355

GnomAD4 exome AF: 0.0407 AC: 56777 AN: 1394110 Hom.: 1546 Cov.: 28 AF XY: 0.0411 AC XY: 28304 AN XY: 688664

Gnomad4 AFR exome AF: 0.157

Gnomad4 AMR exome AF: 0.0253

Gnomad4 ASJ exome AF: 0.0252

Gnomad4 EAS exome AF: 0.0807

Gnomad4 SAS exome AF: 0.0659

Gnomad4 FIN exome AF: 0.0180

Gnomad4 NFE exome AF: 0.0358

Gnomad4 OTH exome AF: 0.0454

GnomAD4 genome AF: 0.0690 AC: 10504 AN: 152308 Hom.: 594 Cov.: 33 AF XY: 0.0680 AC XY: 5066 AN XY: 74476

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.0424

Gnomad4 ASJ AF: 0.0259

Gnomad4 EAS AF: 0.0470

Gnomad4 SAS AF: 0.0634

Gnomad4 FIN AF: 0.0172

Gnomad4 NFE AF: 0.0347

Gnomad4 OTH AF: 0.0614

Alfa AF: 0.0414 Hom.: 222

Bravo AF: 0.0732

Asia WGS AF: 0.0590 AC: 206 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.71
DANN	Benign	0.81

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: rs7995432; hg19: chr13-99573165; COSMIC: COSV59623686;