rs2296994

chr13-98881643-G-Achr13-98881643-G-T

Variant summary

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

The NM_001366683.2(DOCK9):c.2676-16C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,598,088 control chromosomes in the GnomAD database, including 14,532 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 0.12 (1215 hom., cov: 32)
  • Exomes 𝑓: 0.13 (13317 hom.)
• Consequence: DOCK9 NM_001366683.2 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.346

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=-0.54).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK9	NM_001366683.2	c.2676-16C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000682017.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK9	ENST00000682017.1	c.2676-16C>T		splice_polypyrimidine_tract_variant, intron_variant			NM_001366683.2	P3

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18368 AN: 152082 Hom.: 1213 Cov.: 32

Gnomad AFR AF: 0.0744

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.143

GnomAD3 exomes AF: 0.153 AC: 34516 AN: 225958 Hom.: 2886 AF XY: 0.152 AC XY: 18467 AN XY: 121242

Gnomad AFR exome AF: 0.0751

Gnomad AMR exome AF: 0.215

Gnomad ASJ exome AF: 0.151

Gnomad EAS exome AF: 0.200

Gnomad SAS exome AF: 0.194

Gnomad FIN exome AF: 0.120

Gnomad NFE exome AF: 0.132

Gnomad OTH exome AF: 0.144

GnomAD4 exome AF: 0.130 AC: 188313 AN: 1445888 Hom.: 13317 Cov.: 30 AF XY: 0.132 AC XY: 94983 AN XY: 717460

Gnomad4 AFR exome AF: 0.0717

Gnomad4 AMR exome AF: 0.203

Gnomad4 ASJ exome AF: 0.150

Gnomad4 EAS exome AF: 0.242

Gnomad4 SAS exome AF: 0.192

Gnomad4 FIN exome AF: 0.123

Gnomad4 NFE exome AF: 0.120

Gnomad4 OTH exome AF: 0.133

GnomAD4 genome AF: 0.121 AC: 18373 AN: 152200 Hom.: 1215 Cov.: 32 AF XY: 0.122 AC XY: 9094 AN XY: 74422

Gnomad4 AFR AF: 0.0744

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.143

Alfa AF: 0.133 Hom.: 335

Bravo AF: 0.122

Asia WGS AF: 0.204 AC: 706 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	14
Dann	Benign	0.55

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: rs2296994; hg19: chr13-99533897; COSMIC: COSV59630285;