rs7149497

chr14-59310881-A-Cchr14-59310881-A-G

Variant summary

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

The NM_001270520.2(DAAM1):c.274-4399A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 152,064 control chromosomes in the GnomAD database, including 7,421 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 0.29 (7421 hom., cov: 32)
• Consequence: DAAM1 NM_001270520.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.90

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAAM1	NM_001270520.2	c.274-4399A>C		intron_variant		ENST00000360909.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAAM1	ENST00000360909.8	c.274-4399A>C		intron_variant		1	NM_001270520.2	P1
DAAM1	ENST00000395125.1	c.274-4399A>C		intron_variant		1
DAAM1	ENST00000557327.1	n.302-9609A>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43535 AN: 151946 Hom.: 7428 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.286 AC: 43520 AN: 152064 Hom.: 7421 Cov.: 32 AF XY: 0.287 AC XY: 21305 AN XY: 74330

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.288

Gnomad4 EAS AF: 0.562

Gnomad4 SAS AF: 0.387

Gnomad4 FIN AF: 0.335

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.293

Alfa AF: 0.344 Hom.: 11314

Bravo AF: 0.277

Asia WGS AF: 0.464 AC: 1612 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	15
Dann	Benign	0.72

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: rs7149497; hg19: chr14-59777599;