rs1219576861

Variant names:

• chr19-11199532-A-G
• rs1219576861
• NM_020812.4:c.6109T>C

Your query was ambiguous. Multiple possible variants found:

• chr19-11199532-A-G
• chr19-11199532-A-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_020812.4(DOCK6):​c.6109T>C​(p.Leu2037Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DOCK6 NM_020812.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112

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 Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18281248).
• BP7: Synonymous conserved (PhyloP=0.112 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK6	NM_020812.4	c.6109T>C	p.Leu2037Leu	synonymous_variant	Exon 48 of 48	ENST00000294618.12	NP_065863.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK6	ENST00000294618.12	c.6109T>C	p.Leu2037Leu	synonymous_variant	Exon 48 of 48	1	NM_020812.4	ENSP00000294618.6
DOCK6	ENST00000587734.1	c.83T>C	p.Leu28Pro	missense_variant	Exon 2 of 2	5		ENSP00000468291.1
DOCK6	ENST00000587656.6	c.6214T>C	p.Leu2072Leu	synonymous_variant	Exon 49 of 49	5		ENSP00000468638.2
DOCK6	ENST00000586702.1	n.1012T>C		non_coding_transcript_exon_variant	Exon 7 of 7	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1428212 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 706962

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	4.2
DANN	Benign	0.77
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.20	T
MetaRNN	Benign	0.18	T
Sift4G	Pathogenic	0.0	D
MVP		0.69
GERP RS		-5.8

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

LitVar

Other links and lift over

dbSNP: rs1219576861; hg19: chr19-11310208;