14-59323174-G-T

Variant summary

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

The NM_001270520.2(DAAM1):c.723G>T(p.Leu241=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0784 in 1,613,482 control chromosomes in the GnomAD database, including 5,507 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.063 ( 397 hom., cov: 32)

Exomes 𝑓: 0.080 ( 5110 hom. )

Consequence

DAAM1
NM_001270520.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.63

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 14-59323174-G-T is Benign according to our data. Variant chr14-59323174-G-T is described in ClinVar as [Benign]. Clinvar id is 3056313.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.63 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0915 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.723G>T	p.Leu241=	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.723G>T	p.Leu241=	synonymous_variant	6/25	1	NM_001270520.2	P1	Q9Y4D1-2
DAAM1	ENST00000395125.1 linkuse as main transcript	c.723G>T	p.Leu241=	synonymous_variant	5/25	1			Q9Y4D1-1

Frequencies

GnomAD3 genomes

AF:

0.0629

AC:

9572

AN:

152112

Hom.:

397

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0152

Gnomad AMI

AF:

0.0691

Gnomad AMR

AF:

0.0542

Gnomad ASJ

AF:

0.0770

Gnomad EAS

AF:

0.0131

Gnomad SAS

AF:

0.0205

Gnomad FIN

AF:

0.105

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0934

Gnomad OTH

AF:

0.0640

GnomAD3 exomes

AF:

0.0655

AC:

16343

AN:

249502

Hom.:

641

AF XY:

0.0657

AC XY:

8867

AN XY:

134970

show subpopulations

Gnomad AFR exome

AF:

0.0124

Gnomad AMR exome

AF:

0.0423

Gnomad ASJ exome

AF:

0.0776

Gnomad EAS exome

AF:

0.0107

Gnomad SAS exome

AF:

0.0236

Gnomad FIN exome

AF:

0.100

Gnomad NFE exome

AF:

0.0921

Gnomad OTH exome

AF:

0.0774

GnomAD4 exome

AF:

0.0800

AC:

116842

AN:

1461254

Hom.:

5110

Cov.:

AF XY:

0.0786

AC XY:

57113

AN XY:

726864

show subpopulations

Gnomad4 AFR exome

AF:

0.0120

Gnomad4 AMR exome

AF:

0.0434

Gnomad4 ASJ exome

AF:

0.0793

Gnomad4 EAS exome

AF:

0.00984

Gnomad4 SAS exome

AF:

0.0251

Gnomad4 FIN exome

AF:

0.102

Gnomad4 NFE exome

AF:

0.0897

Gnomad4 OTH exome

AF:

0.0732

GnomAD4 genome

AF:

0.0629

AC:

9579

AN:

152228

Hom.:

397

Cov.:

AF XY:

0.0623

AC XY:

4634

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0152

Gnomad4 AMR

AF:

0.0540

Gnomad4 ASJ

AF:

0.0770

Gnomad4 EAS

AF:

0.0131

Gnomad4 SAS

AF:

0.0208

Gnomad4 FIN

AF:

0.105

Gnomad4 NFE

AF:

0.0934

Gnomad4 OTH

AF:

0.0662

Alfa

AF:

0.0786

Hom.:

303

Bravo

AF:

0.0574

Asia WGS

AF:

0.0420

AC:

146

AN:

3478

EpiCase

AF:

0.0902

EpiControl

AF:

0.0849

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 30, 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

-0.44

Cadd

Benign

6.4

Dann

Benign

0.67

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