rs12042319

Variant names:

• chr1-62584148-G-A
• rs12042319
• NM_001367561.1:c.1801-894C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-62584148-G-A
• chr1-62584148-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001367561.1(DOCK7):​c.1801-894C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 976,538 control chromosomes in the GnomAD database, including 61,061 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (9789 hom., cov: 32)
  • Exomes 𝑓: 0.35 (51272 hom.)
• Consequence: DOCK7 NM_001367561.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0950
• Publications: 24 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-62584148-G-A is Benign according to our data. Variant chr1-62584148-G-A is described in ClinVar as Benign. ClinVar VariationId is 1296204.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK7	NM_001367561.1	c.1801-894C>T		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.1801-894C>T		intron_variant	Intron 15 of 49	5	NM_001367561.1	ENSP00000489124.1

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53555 AN: 151802 Hom.: 9776 Cov.: 32

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.307

GnomAD4 exome AF: 0.351 AC: 289042 AN: 824618 Hom.: 51272 Cov.: 24 AF XY: 0.351 AC XY: 133844 AN XY: 381056

African (AFR) AF: 0.446 AC: 6949 AN: 15594

American (AMR) AF: 0.345 AC: 337 AN: 978

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 1105 AN: 5106

East Asian (EAS) AF: 0.203 AC: 733 AN: 3610

South Asian (SAS) AF: 0.422 AC: 6858 AN: 16258

European-Finnish (FIN) AF: 0.265 AC: 72 AN: 272

Middle Eastern (MID) AF: 0.314 AC: 503 AN: 1602

European-Non Finnish (NFE) AF: 0.349 AC: 263220 AN: 754158

Other (OTH) AF: 0.343 AC: 9265 AN: 27040

GnomAD4 genome AF: 0.353 AC: 53605 AN: 151920 Hom.: 9789 Cov.: 32 AF XY: 0.350 AC XY: 26029 AN XY: 74272

African (AFR) AF: 0.442 AC: 18290 AN: 41424

American (AMR) AF: 0.342 AC: 5229 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 803 AN: 3472

East Asian (EAS) AF: 0.189 AC: 975 AN: 5152

South Asian (SAS) AF: 0.422 AC: 2031 AN: 4814

European-Finnish (FIN) AF: 0.251 AC: 2648 AN: 10564

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.332 AC: 22520 AN: 67910

Other (OTH) AF: 0.314 AC: 661 AN: 2104

Alfa AF: 0.340 Hom.: 5623

Bravo AF: 0.363

Asia WGS AF: 0.367 AC: 1275 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Mar 14, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.17
PhyloP100		0.095
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: rs12042319; hg19: chr1-63049819;