rs541344421

chr1-62625414-TA-Tchr1-62625414-TA-TAA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001367561.1(DOCK7):c.1283-14del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00809 in 1,515,688 control chromosomes in the GnomAD database, including 52 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0053 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0084 (50 hom.)
• Consequence: DOCK7 NM_001367561.1 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.26

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 Benign. Variant got -16 ACMG points.

• BP6: Variant 1-62625414-TA-T is Benign according to our data. Variant chr1-62625414-TA-T is described in ClinVar as [Likely_benign]. Clinvar id is 235780.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00533 (804/150782) while in subpopulation NFE AF= 0.00827 (559/67568). AF 95% confidence interval is 0.00771. There are 2 homozygotes in gnomad4. There are 368 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK7	NM_001367561.1	c.1283-14del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000635253.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK7	ENST00000635253.2	c.1283-14del		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001367561.1

Frequencies

GnomAD3 genomes AF: 0.00534 AC: 804 AN: 150676 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00163

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00410

Gnomad ASJ AF: 0.00581

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000838

Gnomad FIN AF: 0.00798

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00827

Gnomad OTH AF: 0.00435

GnomAD3 exomes AF: 0.00659 AC: 1234 AN: 187348 Hom.: 5 AF XY: 0.00682 AC XY: 697 AN XY: 102176

Gnomad AFR exome AF: 0.00148

Gnomad AMR exome AF: 0.00287

Gnomad ASJ exome AF: 0.00832

Gnomad EAS exome AF: 0.000975

Gnomad SAS exome AF: 0.00110

Gnomad FIN exome AF: 0.00816

Gnomad NFE exome AF: 0.00956

Gnomad OTH exome AF: 0.00983

GnomAD4 exome AF: 0.00839 AC: 11457 AN: 1364906 Hom.: 50 Cov.: 30 AF XY: 0.00822 AC XY: 5559 AN XY: 676582

Gnomad4 AFR exome AF: 0.00174

Gnomad4 AMR exome AF: 0.00243

Gnomad4 ASJ exome AF: 0.00644

Gnomad4 EAS exome AF: 0.000320

Gnomad4 SAS exome AF: 0.00132

Gnomad4 FIN exome AF: 0.00789

Gnomad4 NFE exome AF: 0.00974

Gnomad4 OTH exome AF: 0.00705

GnomAD4 genome AF: 0.00533 AC: 804 AN: 150782 Hom.: 2 Cov.: 32 AF XY: 0.00500 AC XY: 368 AN XY: 73618

Gnomad4 AFR AF: 0.00163

Gnomad4 AMR AF: 0.00410

Gnomad4 ASJ AF: 0.00581

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000839

Gnomad4 FIN AF: 0.00798

Gnomad4 NFE AF: 0.00827

Gnomad4 OTH AF: 0.00431

Alfa AF: 0.00504 Hom.: 0

Bravo AF: 0.00499

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Developmental and epileptic encephalopathy, 23 Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 28, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Apr 11, 2023	- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Feb 02, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs541344421; hg19: chr1-63091085;