rs12872448

Positions:

• chr13-98942993-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.243+12442C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,196 control chromosomes in the GnomAD database, including 3,640 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 0.20 (3640 hom., cov: 33)
• Consequence: DOCK9 NM_001366683.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK9	NM_001366683.2	c.243+12442C>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.243+12442C>T		intron_variant			NM_001366683.2	ENSP00000507034	P3

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30618 AN: 152078 Hom.: 3625 Cov.: 33

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.224

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.202 AC: 30681 AN: 152196 Hom.: 3640 Cov.: 33 AF XY: 0.202 AC XY: 15037 AN XY: 74430

Gnomad4 AFR AF: 0.329

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.228

Alfa AF: 0.154 Hom.: 3969

Bravo AF: 0.215

Asia WGS AF: 0.217 AC: 752 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.13
DANN	Benign	0.61

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: rs12872448; hg19: chr13-99595247;