Variant 14-59326037-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001270520.2(DAAM1):c.1134G>A(p.Pro378Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00619 in 1,614,170 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0044 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0064 ( 38 hom. )

Consequence

DAAM1
NM_001270520.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.431

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:

DAAM1 (HGNC:):

DAAM1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 14-59326037-G-A is Benign according to our data. Variant chr14-59326037-G-A is described in ClinVar as [Benign]. Clinvar id is 719367.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.431 with no splicing effect.

BS2

High AC in GnomAd4 at 676 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAAM1	NM_001270520.2 linkuse as main transcript	c.1134G>A	p.Pro378Pro	synonymous_variant	10/25	ENST00000360909.8	NP_001257449.1	Q9Y4D1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DAAM1	ENST00000360909.8 linkuse as main transcript	c.1134G>A	p.Pro378Pro	synonymous_variant	10/25	1	NM_001270520.2	ENSP00000354162.3	Q9Y4D1-2
DAAM1	ENST00000395125.1 linkuse as main transcript	c.1134G>A	p.Pro378Pro	synonymous_variant	9/25	1		ENSP00000378557.1	Q9Y4D1-1
DAAM1	ENST00000556894.1 linkuse as main transcript	n.250G>A		non_coding_transcript_exon_variant	3/3	5

Frequencies

GnomAD3 genomes

AF:

0.00443

AC:

675

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00913

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00689

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00423

AC:

1064

AN:

251366

Hom.:

AF XY:

0.00419

AC XY:

569

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.00178

Gnomad AMR exome

AF:

0.00133

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00905

Gnomad NFE exome

AF:

0.00644

Gnomad OTH exome

AF:

0.00636

GnomAD4 exome

AF:

0.00637

AC:

9319

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00626

AC XY:

4552

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00152

Gnomad4 AMR exome

AF:

0.00148

Gnomad4 ASJ exome

AF:

0.00119

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000591

Gnomad4 FIN exome

AF:

0.00975

Gnomad4 NFE exome

AF:

0.00742

Gnomad4 OTH exome

AF:

0.00583

GnomAD4 genome

AF:

0.00444

AC:

676

AN:

152334

Hom.:

Cov.:

AF XY:

0.00420

AC XY:

313

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00147

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00913

Gnomad4 NFE

AF:

0.00689

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00549

Hom.:

Bravo

AF:

0.00343

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00643

EpiControl

AF:

0.00605

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

DAAM1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 18, 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). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

9.1

DANN

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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