13-98831520-G-A

Variant names:

• chr13-98831520-G-A
• rs2092762323
• NM_001366683.2:c.4463C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001366683.2(DOCK9):​c.4463C>T​(p.Thr1488Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DOCK9 NM_001366683.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.56

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41596532).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK9	NM_001366683.2	c.4463C>T	p.Thr1488Ile	missense_variant	Exon 41 of 53	ENST00000682017.1	NP_001353612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK9	ENST00000682017.1	c.4463C>T	p.Thr1488Ile	missense_variant	Exon 41 of 53		NM_001366683.2	ENSP00000507034.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4397C>T (p.T1466I) alteration is located in exon 41 (coding exon 41) of the DOCK9 gene. This alteration results from a C to T substitution at nucleotide position 4397, causing the threonine (T) at amino acid position 1466 to be replaced by an isoleucine (I). 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	0.50
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.070	.;.;.;.;T
Eigen	Benign	-0.038
Eigen_PC	Benign	0.047
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D;D;D
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.42	T;T;T;T;T
MetaSVM	Benign	-0.61	T
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.8	.;N;.;N;N
REVEL	Benign	0.24
Sift	Benign	0.088	.;T;.;T;T
Sift4G	Benign	0.082	.;T;T;.;D
Polyphen		0.023, 0.033	.;B;.;B;.
Vest4		0.46, 0.38
MVP		0.52
MPC		0.79
ClinPred		0.96	D
GERP RS		5.4
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs2092762323; hg19: chr13-99483774;