13-99087863-T-C

Variant names:

• chr13-99087863-T-C
• rs1927568
• XM_047430231.1:c.80A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_047430231.1(DOCK9):​c.80A>G​(p.His27Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,086 control chromosomes in the GnomAD database, including 6,359 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/4 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.28 (6358 hom., cov: 33)
  • Exomes 𝑓: 0.24 (1 hom.)
• Consequence: DOCK9 XM_047430231.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76
• Publications: 6 publications found

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]

DOCK9-DT (HGNC:43696): (DOCK9 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK9	XM_047430231.1	c.80A>G	p.His27Arg	missense_variant	Exon 1 of 56		XP_047286187.1
DOCK9-DT	NR_047482.1	n.1141T>C		non_coding_transcript_exon_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK9-DT	ENST00000562781.1	n.45T>C		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42585 AN: 151896 Hom.: 6338 Cov.: 33

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.276

GnomAD4 exome AF: 0.236 AC: 17 AN: 72 Hom.: 1 Cov.: 0 AF XY: 0.207 AC XY: 12 AN XY: 58

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.250 AC: 1 AN: 4

European-Non Finnish (NFE) AF: 0.259 AC: 15 AN: 58

Other (OTH) AF: 0.167 AC: 1 AN: 6

GnomAD4 genome AF: 0.280 AC: 42635 AN: 152014 Hom.: 6358 Cov.: 33 AF XY: 0.282 AC XY: 20981 AN XY: 74292

African (AFR) AF: 0.290 AC: 12019 AN: 41480

American (AMR) AF: 0.183 AC: 2802 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1016 AN: 3468

East Asian (EAS) AF: 0.435 AC: 2237 AN: 5146

South Asian (SAS) AF: 0.365 AC: 1757 AN: 4816

European-Finnish (FIN) AF: 0.283 AC: 2991 AN: 10556

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18908 AN: 67950

Other (OTH) AF: 0.277 AC: 586 AN: 2114

Alfa AF: 0.274 Hom.: 13413

Bravo AF: 0.270

Asia WGS AF: 0.352 AC: 1226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.64
PhyloP100		-1.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1927568; hg19: chr13-99740117; COSMIC: COSV59644974;