rs79716948

Positions:

• chr1-62578974-C-A
• chr1-62578974-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2 BP4_Strong BP6_Moderate BS1

The NM_001367561.1(DOCK7):​c.1872-8G>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00618 in 1,193,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (0 hom., cov: 23)
  • Exomes 𝑓: 0.0062 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DOCK7 NM_001367561.1 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.000009257
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.69

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 -8 ACMG points.

• PM2: Variant has high frequency in the AFR(0.0154991) population. However there is too low homozygotes in high coverage region: (expected more than 11, got 0).
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-62578974-C-A is Benign according to our data. Variant chr1-62578974-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 475131.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-62578974-C-A is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00618 (7372/1193442) while in subpopulation AMR AF= 0.0202 (416/20604). AF 95% confidence interval is 0.0186. There are 0 homozygotes in gnomad4_exome. There are 4177 alleles in male gnomad4_exome subpopulation. Median coverage is 27. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK7	NM_001367561.1	c.1872-8G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000635253.2	NP_001354490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK7	ENST00000635253.2	c.1872-8G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_001367561.1	ENSP00000489124

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1229 AN: 79662 Hom.: 0 Cov.: 23 FAILED QC

Gnomad AFR AF: 0.0169

Gnomad AMI AF: 0.0427

Gnomad AMR AF: 0.0113

Gnomad ASJ AF: 0.00740

Gnomad EAS AF: 0.0133

Gnomad SAS AF: 0.00727

Gnomad FIN AF: 0.0283

Gnomad MID AF: 0.0128

Gnomad NFE AF: 0.0151

Gnomad OTH AF: 0.0116

GnomAD4 exome AF: 0.00618 AC: 7372 AN: 1193442 Hom.: 0 Cov.: 27 AF XY: 0.00711 AC XY: 4177 AN XY: 587184

Gnomad4 AFR exome AF: 0.00341

Gnomad4 AMR exome AF: 0.0202

Gnomad4 ASJ exome AF: 0.0129

Gnomad4 EAS exome AF: 0.00677

Gnomad4 SAS exome AF: 0.0182

Gnomad4 FIN exome AF: 0.0697

Gnomad4 NFE exome AF: 0.00244

Gnomad4 OTH exome AF: 0.00436

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0155 AC: 1234 AN: 79692 Hom.: 0 Cov.: 23 AF XY: 0.0162 AC XY: 615 AN XY: 38028

Gnomad4 AFR AF: 0.0170

Gnomad4 AMR AF: 0.0113

Gnomad4 ASJ AF: 0.00740

Gnomad4 EAS AF: 0.0134

Gnomad4 SAS AF: 0.00768

Gnomad4 FIN AF: 0.0283

Gnomad4 NFE AF: 0.0151

Gnomad4 OTH AF: 0.0125

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

Labcorp Genetics (formerly Invitae), Labcorp

Dec 08, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.85
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0000093
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.070		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: rs79716948; hg19: chr1-63044645; COSMIC: COSV52020047;