rs750226687

chr1-62648466-T-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001367561.1(DOCK7):c.468A>G(p.Gln156=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000195 in 1,546,626 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00033 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00018 (0 hom.)
• Consequence: DOCK7 NM_001367561.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.572

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 Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 1-62648466-T-C is Benign according to our data. Variant chr1-62648466-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 571256.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.572 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK7	NM_001367561.1	c.468A>G	p.Gln156=	synonymous_variant	5/50	ENST00000635253.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK7	ENST00000635253.2	c.468A>G	p.Gln156=	synonymous_variant	5/50	5	NM_001367561.1

Frequencies

GnomAD3 genomes AF: 0.000329 AC: 50 AN: 152134 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.00138

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000950 AC: 19 AN: 200008 Hom.: 0 AF XY: 0.000102 AC XY: 11 AN XY: 108024

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000103

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: 0.000173

Gnomad OTH exome AF: 0.000201

GnomAD4 exome AF: 0.000181 AC: 252 AN: 1394492 Hom.: 0 Cov.: 31 AF XY: 0.000179 AC XY: 124 AN XY: 690886

Gnomad4 AFR exome AF: 0.0000322

Gnomad4 AMR exome AF: 0.0000998

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: 0.000225

Gnomad4 OTH exome AF: 0.0000878

GnomAD4 genome AF: 0.000329 AC: 50 AN: 152134 Hom.: 1 Cov.: 32 AF XY: 0.000417 AC XY: 31 AN XY: 74330

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00138

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000159 Hom.: 0

Bravo AF: 0.000268

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Developmental and epileptic encephalopathy, 23 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 11, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	5.7
Dann	Benign	0.36

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: rs750226687; hg19: chr1-63114137; COSMIC: COSV99226764; COSMIC: COSV99226764;