19-11199195-C-T

Variant names:

• chr19-11199195-C-T
• rs12980863
• NM_020812.4:c.*302G>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020812.4(DOCK6):​c.*302G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 369,194 control chromosomes in the GnomAD database, including 31,237 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (12983 hom., cov: 33)
  • Exomes 𝑓: 0.40 (18254 hom.)
• Consequence: DOCK6 NM_020812.4 downstream_gene
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.11

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 19-11199195-C-T is Benign according to our data. Variant chr19-11199195-C-T is described in ClinVar as [Benign]. Clinvar id is 1244507.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK6	NM_020812.4	c.*302G>A		downstream_gene_variant		ENST00000294618.12	NP_065863.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK6	ENST00000294618.12	c.*302G>A		downstream_gene_variant		1	NM_020812.4	ENSP00000294618.6
DOCK6	ENST00000587734.1	c.*123G>A		downstream_gene_variant		5		ENSP00000468291.1
DOCK6	ENST00000586702.1	n.*100G>A		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62595 AN: 151932 Hom.: 12978 Cov.: 33

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.405

GnomAD4 exome AF: 0.403 AC: 87544 AN: 217142 Hom.: 18254 AF XY: 0.406 AC XY: 45661 AN XY: 112522

Gnomad4 AFR exome AF: 0.420

Gnomad4 AMR exome AF: 0.377

Gnomad4 ASJ exome AF: 0.347

Gnomad4 EAS exome AF: 0.376

Gnomad4 SAS exome AF: 0.480

Gnomad4 FIN exome AF: 0.450

Gnomad4 NFE exome AF: 0.396

Gnomad4 OTH exome AF: 0.400

GnomAD4 genome AF: 0.412 AC: 62635 AN: 152052 Hom.: 12983 Cov.: 33 AF XY: 0.414 AC XY: 30759 AN XY: 74328

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.338

Gnomad4 EAS AF: 0.374

Gnomad4 SAS AF: 0.485

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.402

Alfa AF: 0.400 Hom.: 1215

Bravo AF: 0.406

Asia WGS AF: 0.447 AC: 1551 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 08, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.41
DANN	Benign	0.67

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12980863; hg19: chr19-11309871;