1-62648484-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_001367561.1(DOCK7):c.450A>C(p.Gln150His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000218 in 1,376,126 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. Synonymous variant affecting the same amino acid position (i.e. Q150Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: DOCK7 NM_001367561.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54

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 1 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=0.23648602).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK7	NM_001367561.1	c.450A>C	p.Gln150His	missense_variant	5/50	ENST00000635253.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK7	ENST00000635253.2	c.450A>C	p.Gln150His	missense_variant	5/50	5	NM_001367561.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000552 AC: 1 AN: 181218 Hom.: 0 AF XY: 0.0000103 AC XY: 1 AN XY: 97458

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.0000131

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000218 AC: 3 AN: 1376126 Hom.: 0 Cov.: 30 AF XY: 0.00000441 AC XY: 3 AN XY: 681024

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: 0.00000282

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000167 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
Cadd	Benign	21
Dann	Uncertain	1.0
Eigen	Benign	0.032
Eigen_PC	Benign	0.020
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.84	T;T;D;D;D;T;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.24	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.92	L;L;L;L;L;L;L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.8	N;.;N;.;.;.;D
REVEL	Benign	0.26
Sift	Benign	0.42	T;.;T;.;.;.;T
Sift4G	Benign	0.34	T;T;T;T;T;T;T
Polyphen		1.0, 0.045, 1.0	.;D;D;B;D;.;.
Vest4		0.54
MutPred		0.19		Loss of methylation at K147 (P = 0.0638);Loss of methylation at K147 (P = 0.0638);Loss of methylation at K147 (P = 0.0638);Loss of methylation at K147 (P = 0.0638);Loss of methylation at K147 (P = 0.0638);Loss of methylation at K147 (P = 0.0638);Loss of methylation at K147 (P = 0.0638);
MVP		0.76
MPC		0.36
ClinPred		0.33	T
GERP RS		2.0
Varity_R		0.23
gMVP		0.51

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: rs771961808; hg19: chr1-63114155;