14-59323009-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_001270520.2(DAAM1):c.558G>A(p.Lys186=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 1,613,802 control chromosomes in the GnomAD database, including 124,603 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.31 ( 8776 hom., cov: 31)

Exomes 𝑓: 0.39 ( 115827 hom. )

Consequence

DAAM1
NM_001270520.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.10

Variant links:

Genes affected

DAAM1 (HGNC:18142): (dishevelled associated activator of morphogenesis 1) Cell motility, adhesion, cytokinesis, and other functions of the cell cortex are mediated by reorganization of the actin cytoskeleton and several formin homology (FH) proteins have been associated with these processes. The protein encoded by this gene contains two FH domains and belongs to a novel FH protein subfamily implicated in cell polarity. A key regulator of cytoskeletal architecture, the small GTPase Rho, is activated during development by Wnt/Fz signaling to control cell polarity and movement. The protein encoded by this gene is thought to function as a scaffolding protein for the Wnt-induced assembly of a disheveled (Dvl)-Rho complex. This protein also promotes the nucleation and elongation of new actin filaments and regulates cell growth through the stabilization of microtubules. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jul 2012]

DAAM1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 14-59323009-G-A is Benign according to our data. Variant chr14-59323009-G-A is described in ClinVar as [Benign]. Clinvar id is 3060418.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.1 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAAM1	NM_001270520.2 linkuse as main transcript	c.558G>A	p.Lys186=	synonymous_variant	6/25	ENST00000360909.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAAM1	ENST00000360909.8 linkuse as main transcript	c.558G>A	p.Lys186=	synonymous_variant	6/25	1	NM_001270520.2	P1	Q9Y4D1-2
DAAM1	ENST00000395125.1 linkuse as main transcript	c.558G>A	p.Lys186=	synonymous_variant	5/25	1			Q9Y4D1-1
DAAM1	ENST00000557327.1 linkuse as main transcript	n.514G>A		non_coding_transcript_exon_variant	3/3	4

Frequencies

GnomAD3 genomes

AF:

0.312

AC:

47458

AN:

151882

Hom.:

8783

Cov.:

show subpopulations

Gnomad AFR

AF:

0.119

Gnomad AMI

AF:

0.435

Gnomad AMR

AF:

0.281

Gnomad ASJ

AF:

0.325

Gnomad EAS

AF:

0.559

Gnomad SAS

AF:

0.391

Gnomad FIN

AF:

0.415

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.395

Gnomad OTH

AF:

0.313

GnomAD3 exomes

AF:

0.371

AC:

93067

AN:

251156

Hom.:

18622

AF XY:

0.378

AC XY:

51373

AN XY:

135746

show subpopulations

Gnomad AFR exome

AF:

0.115

Gnomad AMR exome

AF:

0.265

Gnomad ASJ exome

AF:

0.324

Gnomad EAS exome

AF:

0.561

Gnomad SAS exome

AF:

0.399

Gnomad FIN exome

AF:

0.410

Gnomad NFE exome

AF:

0.397

Gnomad OTH exome

AF:

0.372

GnomAD4 exome

AF:

0.393

AC:

573874

AN:

1461800

Hom.:

115827

Cov.:

AF XY:

0.393

AC XY:

285689

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.106

Gnomad4 AMR exome

AF:

0.272

Gnomad4 ASJ exome

AF:

0.325

Gnomad4 EAS exome

AF:

0.539

Gnomad4 SAS exome

AF:

0.397

Gnomad4 FIN exome

AF:

0.405

Gnomad4 NFE exome

AF:

0.402

Gnomad4 OTH exome

AF:

0.385

GnomAD4 genome

AF:

0.312

AC:

47445

AN:

152002

Hom.:

8776

Cov.:

AF XY:

0.314

AC XY:

23317

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.119

Gnomad4 AMR

AF:

0.281

Gnomad4 ASJ

AF:

0.325

Gnomad4 EAS

AF:

0.559

Gnomad4 SAS

AF:

0.390

Gnomad4 FIN

AF:

0.415

Gnomad4 NFE

AF:

0.395

Gnomad4 OTH

AF:

0.313

Alfa

AF:

0.366

Hom.:

13761

Bravo

AF:

0.297

Asia WGS

AF:

0.466

AC:

1618

AN:

3478

EpiCase

AF:

0.387

EpiControl

AF:

0.392

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

DAAM1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 31, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

Cadd

Benign

Dann

Benign

0.58

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over