14-59297149-C-T

Variant names:

• chr14-59297149-C-T
• rs12878138
• NM_001270520.2:c.273+5843C>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.273+5843C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0422 in 152,264 control chromosomes in the GnomAD database, including 213 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 0.042 (213 hom., cov: 32)
• Consequence: DAAM1 NM_001270520.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 4 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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.067 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.273+5843C>T		intron	N/A	NP_001257449.1
	DAAM1	NM_014992.2		c.273+5843C>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.273+5843C>T		intron	N/A	ENSP00000354162.3
	DAAM1	ENST00000395125.1	TSL:1	c.273+5843C>T		intron	N/A	ENSP00000378557.1

Frequencies

GnomAD3 genomes AF: 0.0423 AC: 6433 AN: 152146 Hom.: 213 Cov.: 32

Gnomad AFR AF: 0.0119

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.0328

Gnomad ASJ AF: 0.0536

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.0270

Gnomad FIN AF: 0.0235

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0686

Gnomad OTH AF: 0.0489

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

GnomAD4 genome AF: 0.0422 AC: 6430 AN: 152264 Hom.: 213 Cov.: 32 AF XY: 0.0395 AC XY: 2943 AN XY: 74438

African (AFR) AF: 0.0119 AC: 494 AN: 41554

American (AMR) AF: 0.0327 AC: 501 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0536 AC: 186 AN: 3472

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5168

South Asian (SAS) AF: 0.0270 AC: 130 AN: 4818

European-Finnish (FIN) AF: 0.0235 AC: 249 AN: 10614

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0686 AC: 4667 AN: 68024

Other (OTH) AF: 0.0479 AC: 101 AN: 2110

Alfa AF: 0.0486 Hom.: 149

Bravo AF: 0.0431

Asia WGS AF: 0.0160 AC: 56 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.77
DANN	Benign	0.51
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism

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: rs12878138; hg19: chr14-59763867;