14-59337273-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001270520.2(DAAM1):c.1969-2801G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,166 control chromosomes in the GnomAD database, including 3,944 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (3944 hom., cov: 32)
• Consequence: DAAM1 NM_001270520.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.362

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAAM1	NM_001270520.2	c.1969-2801G>T		intron_variant		ENST00000360909.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAAM1	ENST00000360909.8	c.1969-2801G>T		intron_variant		1	NM_001270520.2	P1
DAAM1	ENST00000395125.1	c.1969-1112G>T		intron_variant		1
DAAM1	ENST00000554459.5	n.188-2801G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33867 AN: 152048 Hom.: 3937 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.207

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.223 AC: 33912 AN: 152166 Hom.: 3944 Cov.: 32 AF XY: 0.222 AC XY: 16550 AN XY: 74396

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.209

Alfa AF: 0.126 Hom.: 285

Bravo AF: 0.231

Asia WGS AF: 0.210 AC: 729 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.41
Dann	Benign	0.48

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: rs10873114; hg19: chr14-59803991;