rs1748195

Variant names:

• chr1-62583922-C-G
• rs1748195
• NM_001367561.1:c.1801-668G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-62583922-C-G
• chr1-62583922-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001367561.1(DOCK7):​c.1801-668G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 151,976 control chromosomes in the GnomAD database, including 15,252 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.42 (15252 hom., cov: 33)
• Consequence: DOCK7 NM_001367561.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0810
• Publications: 99 publications found

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]

DOCK7 Gene-Disease associations (from GenCC):

• genetic developmental and epileptic encephalopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• developmental and epileptic encephalopathy, 23

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 1-62583922-C-G is Benign according to our data. Variant chr1-62583922-C-G is described in ClinVar as Benign. ClinVar VariationId is 1251405.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK7	NM_001367561.1	c.1801-668G>C		intron_variant	Intron 15 of 49	ENST00000635253.2	NP_001354490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK7	ENST00000635253.2	c.1801-668G>C		intron_variant	Intron 15 of 49	5	NM_001367561.1	ENSP00000489124.1

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63848 AN: 151858 Hom.: 15209 Cov.: 33

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.421 AC: 63953 AN: 151976 Hom.: 15252 Cov.: 33 AF XY: 0.418 AC XY: 31063 AN XY: 74292

African (AFR) AF: 0.656 AC: 27205 AN: 41494

American (AMR) AF: 0.391 AC: 5974 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 834 AN: 3470

East Asian (EAS) AF: 0.244 AC: 1263 AN: 5178

South Asian (SAS) AF: 0.452 AC: 2180 AN: 4818

European-Finnish (FIN) AF: 0.250 AC: 2637 AN: 10552

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22637 AN: 67896

Other (OTH) AF: 0.367 AC: 770 AN: 2098

Alfa AF: 0.341 Hom.: 5143

Bravo AF: 0.439

Asia WGS AF: 0.440 AC: 1526 AN: 3466

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.36
PhyloP100		-0.081
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: rs1748195; hg19: chr1-63049593;