14-59337273-G-T

Variant names:

• chr14-59337273-G-T
• rs10873114
• NM_001270520.2:c.1969-2801G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270520.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAAM1	NM_001270520.2	MANE Select	c.1969-2801G>T		intron	N/A	NP_001257449.1
	DAAM1	NM_014992.2		c.1969-1112G>T		intron	N/A	NP_055807.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAAM1	ENST00000360909.8	TSL:1 MANE Select	c.1969-2801G>T		intron	N/A	ENSP00000354162.3
	DAAM1	ENST00000395125.1	TSL:1	c.1969-1112G>T		intron	N/A	ENSP00000378557.1
	DAAM1	ENST00000554459.5	TSL:5	n.188-2801G>T		intron	N/A

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

African (AFR) AF: 0.290 AC: 12039 AN: 41508

American (AMR) AF: 0.231 AC: 3538 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 915 AN: 3470

East Asian (EAS) AF: 0.184 AC: 949 AN: 5168

South Asian (SAS) AF: 0.217 AC: 1049 AN: 4828

European-Finnish (FIN) AF: 0.160 AC: 1689 AN: 10588

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13036 AN: 67994

Other (OTH) AF: 0.209 AC: 442 AN: 2114

Alfa AF: 0.131 Hom.: 318

Bravo AF: 0.231

Asia WGS AF: 0.210 AC: 729 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.41
DANN	Benign	0.48
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10873114; hg19: chr14-59803991;