rs17833769

Positions:

• chr14-59188743-C-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001270520.2(DAAM1):​c.-63C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,894 control chromosomes in the GnomAD database, including 2,267 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 0.16 (2253 hom., cov: 32)
  • Exomes 𝑓: 0.21 (14 hom.)
• Consequence: DAAM1 NM_001270520.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAAM1	NM_001270520.2	c.-63C>A		5_prime_UTR_variant	1/25	ENST00000360909.8	NP_001257449.1
DAAM1	XM_005267430.3	c.-63C>A		5_prime_UTR_variant	1/26		XP_005267487.1
DAAM1	XM_005267431.2	c.-209C>A		5_prime_UTR_variant	1/26		XP_005267488.1
DAAM1	XM_047431135.1	c.-209C>A		5_prime_UTR_variant	1/25		XP_047287091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAAM1	ENST00000360909	c.-63C>A		5_prime_UTR_variant	1/25	1	NM_001270520.2	ENSP00000354162.3
DAAM1	ENST00000556596.1	n.98C>A		non_coding_transcript_exon_variant	1/2	1
DAAM1	ENST00000556135.1	c.-63C>A		5_prime_UTR_variant	1/3	3		ENSP00000450498.1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23693 AN: 152082 Hom.: 2256 Cov.: 32

Gnomad AFR AF: 0.0481

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.150

GnomAD4 exome AF: 0.206 AC: 143 AN: 694 Hom.: 14 Cov.: 0 AF XY: 0.192 AC XY: 88 AN XY: 458

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.232

Gnomad4 NFE exome AF: 0.164

Gnomad4 OTH exome AF: 0.188

GnomAD4 genome AF: 0.156 AC: 23676 AN: 152200 Hom.: 2253 Cov.: 32 AF XY: 0.156 AC XY: 11603 AN XY: 74412

Gnomad4 AFR AF: 0.0480

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.157

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.148

Alfa AF: 0.197 Hom.: 4064

Bravo AF: 0.141

Asia WGS AF: 0.187 AC: 651 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Benign	0.94
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17833769; hg19: chr14-59655461;