rs199838752

Variant names:

• chr19-11236849-C-G
• NM_020812.4:c.2104G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-11236849-C-G
• chr19-11236849-C-T

Variant summary

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

The NM_020812.4(DOCK6):​c.2104G>C​(p.Gly702Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000713 in 1,403,206 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: DOCK6 NM_020812.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.16

Genes affected

DOCK6 (HGNC:19189): (dedicator of cytokinesis 6) This gene encodes a member of the dedicator of cytokinesis (DOCK) family of atypical guanine nucleotide exchange factors. Guanine nucleotide exchange factors interact with small GTPases and are components of intracellular signaling networks. The encoded protein is a group C DOCK protein and plays a role in actin cytoskeletal reorganization by activating the Rho GTPases Cdc42 and Rac1. Mutations in this gene are associated with Adams-Oliver syndrome 2. [provided by RefSeq, Dec 2011]

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 rank	MANE	Protein	UniProt
DOCK6	NM_020812.4	c.2104G>C	p.Gly702Arg	missense_variant	Exon 19 of 48	ENST00000294618.12	NP_065863.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK6	ENST00000294618.12	c.2104G>C	p.Gly702Arg	missense_variant	Exon 19 of 48	1	NM_020812.4	ENSP00000294618.6
DOCK6	ENST00000587656.6	c.2104G>C	p.Gly702Arg	missense_variant	Exon 19 of 49	5		ENSP00000468638.2
DOCK6	ENST00000590680.5	c.445G>C	p.Gly149Arg	missense_variant	Exon 5 of 11	5		ENSP00000467191.1
DOCK6	ENST00000591750.1	n.2073G>C		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.13e-7 AC: 1 AN: 1403206 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 692668

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.8	M
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Benign	0.16
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.051	T
Polyphen		0.98	D
Vest4		0.28
MutPred		0.50		Gain of solvent accessibility (P = 0.0014);
MVP		0.68
MPC		0.63
ClinPred		0.99	D
GERP RS		3.6
Varity_R		0.78
gMVP		0.68

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: chr19-11347525;