rs62620184

Variant names:

• chr13-98902367-G-A
• rs62620184
• NM_001366683.2:c.1301C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001366683.2(DOCK9):​c.1301C>T​(p.Ala434Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0437 in 1,613,954 control chromosomes in the GnomAD database, including 1,873 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (136 hom., cov: 33)
  • Exomes 𝑓: 0.045 (1737 hom.)
• Consequence: DOCK9 NM_001366683.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.62

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0022068322).
• BP6: Variant 13-98902367-G-A is Benign according to our data. Variant chr13-98902367-G-A is described in ClinVar as [Benign]. Clinvar id is 402794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK9	NM_001366683.2	c.1301C>T	p.Ala434Val	missense_variant	Exon 12 of 53	ENST00000682017.1	NP_001353612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK9	ENST00000682017.1	c.1301C>T	p.Ala434Val	missense_variant	Exon 12 of 53		NM_001366683.2	ENSP00000507034.1

Frequencies

GnomAD3 genomes AF: 0.0336 AC: 5109 AN: 152186 Hom.: 135 Cov.: 33

Gnomad AFR AF: 0.00866

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0361

Gnomad ASJ AF: 0.0533

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0830

Gnomad FIN AF: 0.0400

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0446

Gnomad OTH AF: 0.0344

GnomAD3 exomes AF: 0.0432 AC: 10763 AN: 249154 Hom.: 336 AF XY: 0.0468 AC XY: 6330 AN XY: 135178

Gnomad AFR exome AF: 0.00684

Gnomad AMR exome AF: 0.0262

Gnomad ASJ exome AF: 0.0512

Gnomad EAS exome AF: 0.000835

Gnomad SAS exome AF: 0.0895

Gnomad FIN exome AF: 0.0395

Gnomad NFE exome AF: 0.0473

Gnomad OTH exome AF: 0.0481

GnomAD4 exome AF: 0.0448 AC: 65431 AN: 1461650 Hom.: 1737 Cov.: 32 AF XY: 0.0463 AC XY: 33647 AN XY: 727116

Gnomad4 AFR exome AF: 0.00857

Gnomad4 AMR exome AF: 0.0264

Gnomad4 ASJ exome AF: 0.0534

Gnomad4 EAS exome AF: 0.000453

Gnomad4 SAS exome AF: 0.0868

Gnomad4 FIN exome AF: 0.0391

Gnomad4 NFE exome AF: 0.0447

Gnomad4 OTH exome AF: 0.0457

GnomAD4 genome AF: 0.0336 AC: 5110 AN: 152304 Hom.: 136 Cov.: 33 AF XY: 0.0340 AC XY: 2535 AN XY: 74462

Gnomad4 AFR AF: 0.00866

Gnomad4 AMR AF: 0.0360

Gnomad4 ASJ AF: 0.0533

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0836

Gnomad4 FIN AF: 0.0400

Gnomad4 NFE AF: 0.0446

Gnomad4 OTH AF: 0.0327

Alfa AF: 0.0408 Hom.: 229

Bravo AF: 0.0308

TwinsUK AF: 0.0464 AC: 172

ALSPAC AF: 0.0423 AC: 163

ESP6500AA AF: 0.00869 AC: 37

ESP6500EA AF: 0.0455 AC: 386

ExAC AF: 0.0447 AC: 5411

Asia WGS AF: 0.0370 AC: 129 AN: 3478

EpiCase AF: 0.0465

EpiControl AF: 0.0479

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	.;.;.;.;T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.85	D;D;D;D;D
MetaRNN	Benign	0.0022	T;T;T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.1	N;N;N;.;.
REVEL	Benign	0.035
Sift	Benign	0.14	T;T;T;.;.
Sift4G	Benign	0.25	.;T;T;T;T
Polyphen		0.0	.;B;.;.;.
Vest4		0.11, 0.082, 0.14, 0.13
MPC		0.30
ClinPred		0.0030	T
GERP RS		0.31
gMVP		0.12

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: rs62620184; hg19: chr13-99554621;