chr13-98884963-G-T

Position:

• chr13-98884963-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001366683.2(DOCK9):​c.2382+8C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.762 in 1,609,406 control chromosomes in the GnomAD database, including 470,729 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.71 (39013 hom., cov: 32)
  • Exomes 𝑓: 0.77 (431716 hom.)
• Consequence: DOCK9 NM_001366683.2 splice_region, intron
• Scores: Splicing: ADA: 0.00005738
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790

Genes affected

DOCK9 (HGNC:14132): (dedicator of cytokinesis 9) Enables cadherin binding activity. Predicted to be involved in positive regulation of GTPase activity. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK9	NM_001366683.2	c.2382+8C>A		splice_region_variant, intron_variant		ENST00000682017.1	NP_001353612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK9	ENST00000682017.1	c.2382+8C>A		splice_region_variant, intron_variant			NM_001366683.2	ENSP00000507034.1

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107775 AN: 151914 Hom.: 38996 Cov.: 32

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.786

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.712

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.760

GnomAD3 exomes AF: 0.746 AC: 182181 AN: 244286 Hom.: 68963 AF XY: 0.754 AC XY: 99871 AN XY: 132450

Gnomad AFR exome AF: 0.581

Gnomad AMR exome AF: 0.768

Gnomad ASJ exome AF: 0.789

Gnomad EAS exome AF: 0.512

Gnomad SAS exome AF: 0.843

Gnomad FIN exome AF: 0.718

Gnomad NFE exome AF: 0.773

Gnomad OTH exome AF: 0.770

GnomAD4 exome AF: 0.768 AC: 1118596 AN: 1457374 Hom.: 431716 Cov.: 40 AF XY: 0.770 AC XY: 557878 AN XY: 724672

Gnomad4 AFR exome AF: 0.579

Gnomad4 AMR exome AF: 0.767

Gnomad4 ASJ exome AF: 0.795

Gnomad4 EAS exome AF: 0.583

Gnomad4 SAS exome AF: 0.841

Gnomad4 FIN exome AF: 0.722

Gnomad4 NFE exome AF: 0.776

Gnomad4 OTH exome AF: 0.762

GnomAD4 genome AF: 0.709 AC: 107830 AN: 152032 Hom.: 39013 Cov.: 32 AF XY: 0.708 AC XY: 52622 AN XY: 74334

Gnomad4 AFR AF: 0.587

Gnomad4 AMR AF: 0.755

Gnomad4 ASJ AF: 0.786

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.827

Gnomad4 FIN AF: 0.712

Gnomad4 NFE AF: 0.771

Gnomad4 OTH AF: 0.760

Alfa AF: 0.748 Hom.: 23625

Bravo AF: 0.710

Asia WGS AF: 0.699 AC: 2428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.49
DANN	Benign	0.27

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000057
dbscSNV1_RF	Benign	0.0
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: rs2274642; hg19: chr13-99537217;