X-118561464-T-A

Position:

• chrX-118561464-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_144658.4(DOCK11):​c.640T>A​(p.Ser214Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: DOCK11 NM_144658.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.60

Genes affected

DOCK11 (HGNC:23483): (dedicator of cytokinesis 11) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in several processes, including marginal zone B cell differentiation; positive regulation of GTPase activity; and positive regulation of filopodium assembly. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK11	NM_144658.4	c.640T>A	p.Ser214Thr	missense_variant	7/53	ENST00000276202.9	NP_653259.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK11	ENST00000276202.9	c.640T>A	p.Ser214Thr	missense_variant	7/53	1	NM_144658.4	ENSP00000276202.7
DOCK11	ENST00000276204.10	c.640T>A	p.Ser214Thr	missense_variant	7/53	5		ENSP00000276204.6
DOCK11	ENST00000633080.1	c.88T>A	p.Ser30Thr	missense_variant	2/49	5		ENSP00000487829.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 22

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

Feb 06, 2024

The c.640T>A (p.S214T) alteration is located in exon 7 (coding exon 7) of the DOCK11 gene. This alteration results from a T to A substitution at nucleotide position 640, causing the serine (S) at amino acid position 214 to be replaced by a threonine (T). 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	Benign	0.091
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.23	.;T;T
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Uncertain	0.23	D
MetaRNN	Uncertain	0.49	T;T;T
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Uncertain	2.4	.;M;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.6	N;N;.
REVEL	Uncertain	0.39
Sift	Benign	0.14	T;T;.
Sift4G	Uncertain	0.022	D;D;D
Polyphen		0.010	.;B;.
Vest4		0.26
MutPred		0.32		Loss of ubiquitination at K218 (P = 0.0738);Loss of ubiquitination at K218 (P = 0.0738);.;
MVP		0.80
MPC		0.40
ClinPred		0.89	D
GERP RS		5.4
Varity_R		0.36
gMVP		0.71

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: chrX-117695427;