chr13-98797209-C-A

Position:

• chr13-98797209-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_001366683.2(DOCK9):​c.6062G>T​(p.Arg2021Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DOCK9 NM_001366683.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DOCK9. . Gene score misZ 3.0983 (greater than the threshold 3.09). Trascript score misZ 3.4483 (greater than threshold 3.09). GenCC has associacion of gene with keratoconus.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK9	NM_001366683.2	c.6062G>T	p.Arg2021Leu	missense_variant	52/53	ENST00000682017.1	NP_001353612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK9	ENST00000682017.1	c.6062G>T	p.Arg2021Leu	missense_variant	52/53		NM_001366683.2	ENSP00000507034.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 05, 2024

The c.6107G>T (p.R2036L) alteration is located in exon 55 (coding exon 55) of the DOCK9 gene. This alteration results from a G to T substitution at nucleotide position 6107, causing the arginine (R) at amino acid position 2036 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	27
DANN	Uncertain	1.0
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.99	D;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.72	D;D;D
MetaSVM	Benign	-0.76	T
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-4.9	.;D;.
REVEL	Uncertain	0.51
Sift	Uncertain	0.0020	.;D;.
Sift4G	Uncertain	0.0070	.;D;D
Polyphen		0.99	.;D;.
Vest4		0.81, 0.78
MVP		0.60
MPC		1.1
ClinPred		1.0	D
GERP RS		5.5
gMVP		0.86

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-99449463;