1-62625414-TA-TAA

Position:

• chr1-62625414-TA-TAA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP6_Moderate BS1

The NM_001367561.1(DOCK7):​c.1283-14dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000853 in 1,511,166 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00062 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00088 (0 hom.)
• Consequence: DOCK7 NM_001367561.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 1-62625414-T-TA is Benign according to our data. Variant chr1-62625414-T-TA is described in ClinVar as [Benign]. Clinvar id is 1604867.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000878 (1195/1360382) while in subpopulation AFR AF= 0.00252 (75/29816). AF 95% confidence interval is 0.00206. There are 0 homozygotes in gnomad4_exome. There are 615 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK7	NM_001367561.1	c.1283-14dupT		intron_variant		ENST00000635253.2	NP_001354490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK7	ENST00000635253.2	c.1283-14dupT		intron_variant		5	NM_001367561.1	ENSP00000489124.1

Frequencies

GnomAD3 genomes AF: 0.000624 AC: 94 AN: 150678 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00192

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000596

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000388

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000296

Gnomad OTH AF: 0.000483

GnomAD4 exome AF: 0.000878 AC: 1195 AN: 1360382 Hom.: 0 Cov.: 30 AF XY: 0.000912 AC XY: 615 AN XY: 674520

Gnomad4 AFR exome AF: 0.00252

Gnomad4 AMR exome AF: 0.00150

Gnomad4 ASJ exome AF: 0.000909

Gnomad4 EAS exome AF: 0.000830

Gnomad4 SAS exome AF: 0.00202

Gnomad4 FIN exome AF: 0.000879

Gnomad4 NFE exome AF: 0.000713

Gnomad4 OTH exome AF: 0.00124

GnomAD4 genome AF: 0.000623 AC: 94 AN: 150784 Hom.: 0 Cov.: 32 AF XY: 0.000530 AC XY: 39 AN XY: 73618

Gnomad4 AFR AF: 0.00192

Gnomad4 AMR AF: 0.000595

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000389

Gnomad4 SAS AF: 0.000210

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000296

Gnomad4 OTH AF: 0.000478

Bravo AF: 0.000748

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Developmental and epileptic encephalopathy, 23 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 30, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;