NM_001290223.2:c.*384A>T

Variant names:

• chr10-127451811-A-T
• rs3740543
• NM_001290223.2:c.*384A>T

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.*384A>T variant causes a 3 prime UTR 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: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DOCK1 NM_001290223.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.433
• Publications: 12 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]

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=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK1	NM_001290223.2	c.*384A>T		3_prime_UTR_variant	Exon 52 of 52	ENST00000623213.2	NP_001277152.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK1	ENST00000623213.2	c.*384A>T		3_prime_UTR_variant	Exon 52 of 52	1	NM_001290223.2	ENSP00000485033.1
DOCK1	ENST00000280333.9	c.*384A>T		3_prime_UTR_variant	Exon 52 of 52	1		ENSP00000280333.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 120066 Hom.: 0 Cov.: 2 AF XY: 0.00 AC XY: 0 AN XY: 63276

African (AFR) AF: 0.00 AC: 0 AN: 3648

American (AMR) AF: 0.00 AC: 0 AN: 3582

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3146

East Asian (EAS) AF: 0.00 AC: 0 AN: 3432

South Asian (SAS) AF: 0.00 AC: 0 AN: 20074

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6886

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 502

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 72308

Other (OTH) AF: 0.00 AC: 0 AN: 6488

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.7
DANN	Benign	0.76
PhyloP100		-0.43

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: rs3740543; hg19: chr10-129250075;