NM_001363540.2:c.37+49780T>G

Variant names:

• chr7-112156322-A-C
• rs2217262
• NM_001363540.2:c.37+49780T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001363540.2(DOCK4):​c.37+49780T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0734 in 152,298 control chromosomes in the GnomAD database, including 478 homozygotes. 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: 𝑓 0.073 (478 hom., cov: 32)
• Consequence: DOCK4 NM_001363540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.905
• Publications: 4 publications found

Genes affected

DOCK4 (HGNC:19192): (dedicator of cytokinesis 4) This gene is a member of the dedicator of cytokinesis (DOCK) family and encodes a protein with a DHR-1 (CZH-1) domain, a DHR-2 (CZH-2) domain and an SH3 domain. This membrane-associated, cytoplasmic protein functions as a guanine nucleotide exchange factor and is involved in regulation of adherens junctions between cells. Mutations in this gene have been associated with ovarian, prostate, glioma, and colorectal cancers. Alternatively spliced variants which encode different protein isoforms have been described, but only one has been fully characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK4	NM_001363540.2	c.37+49780T>G		intron_variant	Intron 1 of 52	ENST00000428084.6	NP_001350469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK4	ENST00000428084.6	c.37+49780T>G		intron_variant	Intron 1 of 52	5	NM_001363540.2	ENSP00000410746.1
DOCK4	ENST00000437633.6	c.37+49780T>G		intron_variant	Intron 1 of 51	1		ENSP00000404179.1
DOCK4	ENST00000476846.5	n.293+49780T>G		intron_variant	Intron 1 of 22	5
DOCK4	ENST00000661654.1	n.306+49780T>G		intron_variant	Intron 1 of 11

Frequencies

GnomAD3 genomes AF: 0.0734 AC: 11172 AN: 152180 Hom.: 477 Cov.: 32

Gnomad AFR AF: 0.0643

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.0619

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0579

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0663

Gnomad OTH AF: 0.0627

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0734 AC: 11175 AN: 152298 Hom.: 478 Cov.: 32 AF XY: 0.0754 AC XY: 5615 AN XY: 74462

African (AFR) AF: 0.0642 AC: 2666 AN: 41558

American (AMR) AF: 0.132 AC: 2020 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0608 AC: 211 AN: 3472

East Asian (EAS) AF: 0.0618 AC: 321 AN: 5192

South Asian (SAS) AF: 0.123 AC: 596 AN: 4830

European-Finnish (FIN) AF: 0.0579 AC: 614 AN: 10612

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0663 AC: 4511 AN: 68038

Other (OTH) AF: 0.0649 AC: 137 AN: 2112

Alfa AF: 0.0701 Hom.: 741

Bravo AF: 0.0777

Asia WGS AF: 0.137 AC: 475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.2
DANN	Benign	0.54
PhyloP100		0.91
Mutation Taster		=100/0	polymorphism (auto)

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: rs2217262; hg19: chr7-111796377;