rs150032045

Positions:

• chr1-62555843-G-C
• chr1-62555843-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP2 BP4

The NM_001367561.1(DOCK7):​c.2578C>G​(p.Pro860Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,459,618 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P860T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: DOCK7 NM_001367561.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.57

Genes affected

DOCK7 (HGNC:19190): (dedicator of cytokinesis 7) The protein encoded by this gene is a guanine nucleotide exchange factor (GEF) that plays a role in axon formation and neuronal polarization. The encoded protein displays GEF activity toward RAC1 and RAC3 Rho small GTPases but not toward CDC42. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, DOCK7
• BP4: Computational evidence support a benign effect (MetaRNN=0.3364888).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK7	NM_001367561.1	c.2578C>G	p.Pro860Ala	missense_variant	21/50	ENST00000635253.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK7	ENST00000635253.2	c.2578C>G	p.Pro860Ala	missense_variant	21/50	5	NM_001367561.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000803 AC: 2 AN: 249186 Hom.: 0 AF XY: 0.00000743 AC XY: 1 AN XY: 134660

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000295

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1459618 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2 AN XY: 725940

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000226

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	23
DANN	Benign	0.97
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.97	D;D;D;D;D;D;D
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.34	T;T;T;T;T;T;T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	1.5	L;L;L;L;L;L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.3	D;.;D;.;.;.;.
REVEL	Benign	0.15
Sift	Benign	0.051	T;.;T;.;.;.;.
Sift4G	Benign	0.18	T;T;T;T;T;T;.
Polyphen		0.015	B;B;P;P;P;.;.
Vest4		0.63
MutPred		0.40		Loss of glycosylation at P860 (P = 0.0079);Loss of glycosylation at P860 (P = 0.0079);Loss of glycosylation at P860 (P = 0.0079);Loss of glycosylation at P860 (P = 0.0079);Loss of glycosylation at P860 (P = 0.0079);Loss of glycosylation at P860 (P = 0.0079);.;
MVP		0.42
MPC		0.41
ClinPred		0.37	T
GERP RS		5.5
Varity_R		0.32
gMVP		0.55

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: rs150032045; hg19: chr1-63021514;