rs1998864

Variant names:

• chr10-127381475-T-A
• rs1998864
• NM_001290223.2:c.3807+107T>A

Your query was ambiguous. Multiple possible variants found:

• chr10-127381475-T-A
• chr10-127381475-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001290223.2(DOCK1):​c.3807+107T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000158 in 761,290 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.000016 (0 hom.)
• Consequence: DOCK1 NM_001290223.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.342
• Publications: 0 publications found

Genes affected

DOCK1 (HGNC:2987): (dedicator of cytokinesis 1) This gene encodes a member of the dedicator of cytokinesis protein family. Dedicator of cytokinesis proteins act as guanine nucleotide exchange factors for small Rho family G proteins. The encoded protein regulates the small GTPase Rac, thereby influencing several biological processes, including phagocytosis and cell migration. Overexpression of this gene has also been associated with certain cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ENSG00000298283 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290223.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK1	NM_001290223.2	MANE Select	c.3807+107T>A		intron	N/A	NP_001277152.2
	DOCK1	NM_001377543.1		c.3744+107T>A		intron	N/A	NP_001364472.1
	DOCK1	NM_001377544.1		c.3780+107T>A		intron	N/A	NP_001364473.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK1	ENST00000623213.2	TSL:1 MANE Select	c.3807+107T>A		intron	N/A	ENSP00000485033.1
	DOCK1	ENST00000280333.9	TSL:1	c.3744+107T>A		intron	N/A	ENSP00000280333.6
	ENSG00000298283	ENST00000754441.1		n.201-2288A>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000158 AC: 12 AN: 761290 Hom.: 0 AF XY: 0.0000104 AC XY: 4 AN XY: 383666

African (AFR) AF: 0.00 AC: 0 AN: 17680

American (AMR) AF: 0.00 AC: 0 AN: 18840

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15968

East Asian (EAS) AF: 0.00 AC: 0 AN: 31892

South Asian (SAS) AF: 0.00 AC: 0 AN: 38218

European-Finnish (FIN) AF: 0.0000261 AC: 1 AN: 38260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3798

European-Non Finnish (NFE) AF: 0.0000196 AC: 11 AN: 561720

Other (OTH) AF: 0.00 AC: 0 AN: 34914

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 250

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.0
DANN	Benign	0.78
PhyloP100		-0.34

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

Other links and lift over

dbSNP: rs1998864; hg19: chr10-129179739;