13-98850006-G-A

Position:

• chr13-98850006-G-A

Variant summary

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

The NM_001366683.2(DOCK9):​c.4013+41C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0588 in 1,415,940 control chromosomes in the GnomAD database, including 3,695 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 0.051 (341 hom., cov: 32)
  • Exomes 𝑓: 0.060 (3354 hom.)
• Consequence: DOCK9 NM_001366683.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.601

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=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK9	NM_001366683.2	c.4013+41C>T		intron_variant		ENST00000682017.1	NP_001353612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK9	ENST00000682017.1	c.4013+41C>T		intron_variant			NM_001366683.2	ENSP00000507034	P3

Frequencies

GnomAD3 genomes AF: 0.0515 AC: 7822 AN: 151994 Hom.: 339 Cov.: 32

Gnomad AFR AF: 0.0156

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.0915

Gnomad ASJ AF: 0.0591

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.0413

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0496

Gnomad OTH AF: 0.0688

GnomAD3 exomes AF: 0.0820 AC: 13162 AN: 160464 Hom.: 785 AF XY: 0.0798 AC XY: 6767 AN XY: 84816

Gnomad AFR exome AF: 0.0152

Gnomad AMR exome AF: 0.167

Gnomad ASJ exome AF: 0.0639

Gnomad EAS exome AF: 0.179

Gnomad SAS exome AF: 0.0998

Gnomad FIN exome AF: 0.0414

Gnomad NFE exome AF: 0.0504

Gnomad OTH exome AF: 0.0721

GnomAD4 exome AF: 0.0597 AC: 75417 AN: 1263826 Hom.: 3354 Cov.: 18 AF XY: 0.0607 AC XY: 38257 AN XY: 630180

Gnomad4 AFR exome AF: 0.0141

Gnomad4 AMR exome AF: 0.154

Gnomad4 ASJ exome AF: 0.0665

Gnomad4 EAS exome AF: 0.238

Gnomad4 SAS exome AF: 0.103

Gnomad4 FIN exome AF: 0.0406

Gnomad4 NFE exome AF: 0.0481

Gnomad4 OTH exome AF: 0.0616

GnomAD4 genome AF: 0.0514 AC: 7826 AN: 152114 Hom.: 341 Cov.: 32 AF XY: 0.0540 AC XY: 4018 AN XY: 74362

Gnomad4 AFR AF: 0.0156

Gnomad4 AMR AF: 0.0917

Gnomad4 ASJ AF: 0.0591

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.0413

Gnomad4 NFE AF: 0.0496

Gnomad4 OTH AF: 0.0691

Alfa AF: 0.0571 Hom.: 104

Bravo AF: 0.0581

Asia WGS AF: 0.148 AC: 514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.6
DANN	Benign	0.70

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: rs2296990; hg19: chr13-99502260; COSMIC: COSV59630276; COSMIC: COSV59630276;